Presentation on theme: "Basic functions of cells"— Presentation transcript:
1Basic functions of cells Instructor: Li LiDepartment of PhysiologyJining medical collegeOffice: 0850 physiological sciences
2Basic functions of cells ⑴ Structure of cell membrane and membrane transport.⑵ Signal transduction of cell membrane.⑶ Membrane potentials and action potentials.
3⑴ Structure of Cell Membrane and Membrane Transport Membranous structure.Transport of substance through the cell membrane.① Simple diffusion.② Protein-Mediated transport.Facilitated diffusion and active transport.③ Endocytosis and exocytosis.
8Membranous Structure Structure ( fluid mosaic model) ① Composed of mainly lipids and proteins.② Lipid bilayer with proteins embedded in a lipid matrix.③ Carbohydrate groups attached to proteins and lipids.④ Cholesterol is inserted into the lipid bilayer.
9Figure The lipid bilayer. hydrophilichydrophobicFigure The lipid bilayer.
13Proteins Integral proteins Peripheral proteins Amphipathic Proteins can function as carrier, channel, ion pump( integral proteins) and enzyme and some controllers of intracellular function( peripheral proteins).ProteinsIntegral proteinsPeripheral proteinsAmphipathicNot amphipathic
14Figure Carbohydrates in the membrane. Identify and interactFigure Carbohydrates in the membrane.
16Transport of Substance Through the Cell Membrane Simple DiffusionProtein-Mediated Transport① Facilitated diffusion via carrier.② Facilitated diffusion via ion channel.③ Primary active transport.④ Secondary active transport.Endocytosis and Exocytosis
17Figure Process of simple diffusion. Random thermal motionSimple diffusionFigure Process of simple diffusion.
18Transport of Substance Through the Cell Membrane Simple DiffusionThe movement of molecules from one region to another solely as a result of their random thermal motion is known as simple diffusion.① Molecules move from an area of higher concentration to lower concentration, and simple diffusion is not coupled with energy( passive transport).② The magnitude of the net flux depends on: concentration difference; temperature; mass of the molecule; surface area; lipid solubility of the molecule.③ Small non-polar substances (oxygen, carbon dioxide, fatty acids, and steroid hormones) can diffuse easily through the membrane.
19Figure Different permeability across the membrane. InsideOutsideNonpolar moleculesPolar moleculesFigure Different permeability across the membrane.The major factor limiting diffusion across a membrane is the hydrophobic interior of its lipid bilayer.
20Figure The net flux by simple diffusion. Temperature
22Transport of Substance Through the Cell Membrane Protein-mediated transportThe transport of slight polar molecules or charged ions is mediated by proteins within the membrane.Facility diffusion① Not energy (ATP) dependent.② Move molecules from a higher to a lower concentration ( passive transport).③ Movement of molecules depends on the concentration gradient( energy source).④ Facilitated diffusion via carrier( transporter is carrier) and facilitated diffusion via channel( transporter is channel).
23Transport of Substance Through the Cell Membrane Protein-mediated transportFacilitated diffusion via carrierCharacteristics:① Glucose and amino acid can be transported via carrier.② Specificity.③ Competition.④ Saturation.
26Figure The saturation of facilitated diffusion via carrier.
27Transport of Substance Through the Cell Membrane Protein-mediated transportFacilitated diffusion via channelCharacteristics:① Charged ions such as sodium, potassium, chloride ,calcium can be transported via channel.② The direction and magnitude of ion flux depend on both the concentration difference and electrical difference ( electrochemical gradient).③ Selectivity determined by size of pore and/or charges lining the inside of channel .④ Ion channel can exist in an open or closed state, and the process of opening and closing ion channel is known as channel gating.⑤ There is three type of channel: voltage-gated; chemically-gated, mechanically-gated.
29electrochemical gradient: The direction and magnitude of ion flux depend on both the concentration difference and electrical difference.
30Figure Selectivity of the ion channel. Selectivity determined by size of pore and/or charges lining the inside of channel .
31Transport of Substance Through the Cell Membrane Protein-mediated transportActive transportActive transport uses energy to move a substance uphill across a membrane( against the substance’s electrochemical gradient), and they are often referred to as “pumps”.① Primary active transport: energy is derived from breakdown of ATP.② Secondary active transport: energy is derived from ion concentration difference across a membrane, which is already created by primary active transport.
32Transport of Substance Through the Cell Membrane Protein-mediated transportPrimary active transportSodium-potassium pumpFunction:① Three sodium ions out of cell and two potassium ions in.② Maintain the characteristic distribution of high intracellular potassium and low intracellular sodium.③ Important for cell volume control.④ The sodium gradient created by this pump is used for secondary active transport.
33Figure Process of primary active transport. Na+ more concentratedK+ more concentrated
35Figure Sodium and volume of cell. Extracellular fluidIntracellular fluidSodium ionWaterFigure Sodium and volume of cell.
36Transport of Substance Through the Cell Membrane Protein-mediated transportSecondary active transportsodium-coupled secondary active transport:① ATP is not used directly.② Depends on primary active transport mechanisms to create a concentration gradient.③ Movement of sodium is always downhill, while the movement of actively transported solute on the same transporter is uphill.④ There are symport( in the same direction as sodium) and antiport( in the opposite direction).
40Transport of Substance Through the Cell Membrane Endocytosis and ExocytosisVery large molecules or particles enter or leave the cell by a specialized function of the cell membrane called endocytosis or exocytosis respectively.EndocytosisPrinciple form:① Phagocytosis: only certain cell show the capability.② Pinocytosis: ① most cell show the capability;② the only way of large molecules such as protein entering the cell.
41Figure Process of phagocytosis. The membrane may be internalized?Figure Process of phagocytosis.
43Receptor-mediated Endocytosis: The cell membrane is not internalized, because the membrane is replaced by vesicle membrane at about the same rate( recycled).Receptor-mediatedEndocytosis:
44Transport of Substance Through the Cell Membrane Endocytosis and ExocytosisExocytosis① Exocytosis provides a route by which membrane impermeable molecules such as protein synthesized by cells can be secreted into extracellular fluid.② Examples : peptide hormone secretion, neurotransmitter release and so on.③ It is always triggered by stimuli that open calcium channels in most cells.
45Figure Process of exocytosis. ExteriorPlasma membraneInterior③VesicleGolgi apparatus②①Endoplasmic reticulumFigure Process of exocytosis.
47SUMMARY ⑴ Structure of Cell Membrane and Membrane Transport Membranous structure.Transport of substance through the cell membrane.① Simple diffusion.② Protein-Mediated transport.Facilitated diffusion and active transport.③ Endocytosis and exocytosis.
48protein External fluid Internal fluid Much of intercellular communication is mediated by chemical messengers.Lipid insoluble messengerLipid soluble messengerExternal fluidReceptorproteinInternal fluidHypothesis: Maybe some kind of protein can help lipid insoluble messenger to transmit its signal and cause subsequent response.
49Figure Two kinds of route of signal transduction.
51⑵ Signal Transduction of Cell Membrane Signal transduction mediated by G-protein linked receptor.Signal transduction mediated by ionotropic receptor.Signal transduction mediated by enzyme-linked receptor.
52Signal Transduction Mediated by G-protein Linked Receptor Signal molecules involved in the signal transduction.G-protein linked receptor; G protein; G-protein effector; second messenger.Two import pathways of signal transduction mediated by G-protein-linked receptor.① Receptor-G-protein-AC pathway.② Receptor-G-protein-PLC pathway.
53metabotrophic channel G-protein coupled receptormetabotrophic channeloutsideinsideLigand( first messenger)GTPResponsesSecond messengerFigure Process of Signal transduction.
54ResponseproducesSignal moleculeFirst messengerThe process of signal transduction mediated by G-protein-linked receptor:G protein-linked receptorbinds toG proteinactivatesG protein effectoractivatesG-protein linked receptor;G protein;G-protein effector;second messenger.Second messengerproducesTarget proteinalters
56Signal Transduction Mediated by G-protein Linked Receptor Signal molecules involved in the signal transduction.① G-protein linked receptor: 7-trasmembrane receptor.② G protein: bound to the receptor is a protein complex located on the inner surface of the plasma membrane and belonging to the family of heterotrimeric proteins and containing αβγsubunits.③ G protein effector: AC; PLC; GC.④ Second messenger: Substance that enter or are generated in the cytoplasm as a result of receptor activation by the first messengers. cAMP; IP3; DG; cGMP, Calcium ions are all second messenger.
57Signal Transduction Mediated by G-protein Linked Receptor Two import pathways of signal transduction mediated by G-protein-linked receptor.① Receptor-G-protein-AC pathway.② Receptor-G-protein-PLC pathway.
61Figure Contrast of two pathways. ligandG-protein-linked receptorFigure Contrast of two pathways.
62Signal Transduction Mediated by Ionotropic Receptor The protein that acts as the receptor itself constitutes an ion channel.Process① Ligand binds to ionotropic receptor.② Ionotropic receptor is activated and the channel opens.③ Ions flow across membrane which causes the change in the membrane potentail.
63Figure Signal transduction mediated by ionotropic receptor. Ligand-gated channalIonotrophic channelResponse: change in membrane potential.Figure Signal transduction mediated by ionotropic receptor.
64Signal Transduction Mediated by Enzyme-Linked Receptor ① The receptors itself have intrinsic enzyme activity.② There are two important receptors: tyrosine kinase receptor and guanylyl cylase receptor.Tyrosine kinase receptorGuanylyl cylase receptor
69SMMURY ⑵ Signal Transduction of Cell Membrane Signal transduction mediated by G-protein linked receptor.Signal transduction mediated by ionotropic receptor.Signal transduction mediated by enzyme-linked receptor.
70⑶ Membrane Potentials and Action Potentials Resting potential and its originAction potential and its originExcitation and excitability of tissues
71Resting Potential and Its Origin Waveform of the resting potential.Origin of the resting potential.
72Nerve fiber RP Figure Measurement of resting potential. 0 mV -60mV ExperimentelectrodeoutsideinsideVoltmeter0 mV-60mVRPIntracellular recordingindifferentrecordingNerve fiberFigure Measurement of resting potential.
73Resting Potential and Its Origin Waveform of the resting potentialResting potentialAll cells under resting conditions have a potential difference across their plasma membrane with inside of the cell negatively charged with respect to the outside. This potential is the resting membrane potential.The magnitude of the resting potential varies from -100 to -5mV depending upon the type of cell.PolarizationThe steady potential difference with the inside of the cell negatively charged with respect to the outside under resting conditions is also called polarization.How resting potential come into being ( how the potential difference is established )?
74Figure Distribution of ions in the two sides of the membrane. Indifferent electrodeRecording electrodeFigure Distribution of ions in the two sides of the membrane.Movement of ions across the membrane causes the potential difference.
75Resting Potential and Its Origin Origin of the resting potentialMovement of ions across the membrane cause the potential difference.Concentration difference and permeability of ions determine which kind of ions can pass through the membrane and the direction of the movement.The magnitude of resting potential is determined by two factors:① Differences in specific ion concentrations in the intracellular and extracellular fluids.② Differences in membrane permeabilities to the different ions.
77Figure Concentration difference across the membrane. 9:120400440505605220.0002-75+55-60Squid axonFigure Concentration difference across the membrane.
78Cl- K+ Ca2+ Na+ Cl- K+ Organic anions Ca2+ Na+ InsideoutsideCl-Cl-K+K+Organic anionsCa2+Ca2+Na+Na+Figure Distribution of ions in the two sides of the membrane.
79Resting Potential and its Origin Origin of the resting potentialLarge organic anions and Ca2+ are impermeable to the membrane, so the ions that can pass through the membrane is likely :K+ ,Na+, Cl- .SO K+ and Na+ and Cl- may play an important role in the origin of resting potential.Hypothesis: Only K+ is permeable to the membrane.What will happen?
80There are two driving force for ions diffusion: ① Concentration difference.② Electrical potential difference.Electrochemical driving forceConcentration difference make K+ move from the inside of the membrane to the outside.Electrical potential difference caused by diffusion of K+ prevent K+ from moving into the outside.Chemical driving force = electrical driving force.The electrochemical driving force is zero.The membrane potential in this state is called K+ equilibrium potential( Ek ).
81Flash How the K + equilibrium potential is established. Concentration difference driving forceElectrical difference driving force=Nerve fiberinsideoutside1K+20K++-K+ equilibrium potentialThe net flux is zeroFlash How the K + equilibrium potential is established.How the K + equilibrium potential is calculated?
82Resting Potential and its Origin Origin of the resting potentialNernst equationNernst equation describes the equilibrium potential for any ion species.Ek=RTzFIn〔K+〕io(mV)= -75mV(Squid axon)≈ RP(-60mV)So the origin of resting potential is not only caused by the movement of potassium.Hypothesis is not right.
83Resting Potential and its Origin Origin of the resting potentialChord conductance equationEm=gK∑gEKgNaENagClECl+∑g=gK+gNa+gClThe greater the membrane permeability to an ion species, the greater the contribution that ion species will make to the membrane potential.ECl=RPgK>>gNa=0EK≈RP
84EK = ﹥ RP Membrane Inside Outside 20k+ k+ + - + - - + - + - + Na+ 9Na+ Flash Contribution of sodium diffusion to the resting potential.Who maintain the concentration difference?
85+ Figure Contribution of sodium potassium pump to resting potential. Sodium potassium pump causes a continuous loss of positive charges from inside membrane.
86Resting Potential and its Origin Origin of the resting potentialK + move from inside of the cell to the outside under resting condition, which causes the inside of the cell negatively charged with respect to the outside. It is the main factor of the origin of the resting potential.Under resting condition, few Na+ diffuse from outside of the cell to the inside, which also contribute to the origin of the resting potential.Sodium-potassium pump results in the net transfer of positive charge to the outside of the cell, so sodium-potassium also contributes to the origin of the resting potential.
87Action Potential and its Origin Waveform of the typical action potential.Mechanism of the action potential.Ionic basis of the action potential.Propagation of the action potential.
88Figure Measurement of action potential. AP 0mV ExperimentIndifferent electrodeRecording electrodeVoltmeterAP0mVRPNerve fiberstimulator
89Figure Waveform of the typical action potential. depolarizationrepolarizationSpike potentialhyperpolarizationAfter hyperpolarized wavepolarizationFigure Waveform of the typical action potential.
90Action Potential and its Origin Waveform of the typical action potential.TermsPolarization: The resting potential state is called polarization.Depolarization: The membrane potential is less negative than the resting potential.Repolarization: When a membrane potential that has been depolarized returns toward the resting value, it is called repolarization.Hyerpolarization: When a membrane potential is more negative than the resting level, it is called hyperpolarization.Overshoot: Overshoot refers to a reversal of the membrane potential, in other words, the inside of a cell becomes positive relative to the outside.
92Action Potential and its Origin Waveform of the typical action potential.Action potentialDefinitionWhen such cells as neurons are stimulated, there will be rapid and large alterations in the membrane potential, which undergo a process of depolarization, repolarization and then returning to the resting potential. This process is called action potential.ShapeRising phaseFalling phaseAfter hyperpolarized waveSharp spikeSpike potential(Major sign of action potential)
93Action Potential and its Origin Mechanism of the action potential.① As the origin of the resting potential, the changes in membrane potential occur because of change in the permeability of the membrane to ions.② The action potential is initiated by a transient change in membrane ion permeability, which allows sodium and potassium ions to move down their concentration gradients.
94Action Potential and its Origin Ionic basis of the action potential.Rising phaseDepolarization of membraneVoltage-gated sodium channels openStimulusMore Sodium ions move into the cellMembrane becomes more depolarizedThreshold potential is reachedMore sodium channels openThe inside positively chargedMembrane potential overshoots
96Action Potential and its Origin Ionic basis of the action potentialFalling phaseSodium permeability abruptly decreases and voltage-gated potassium channels open, which makes the membrane potential begins to repolarize rapidly to its resting potential.After hyperpolarized waveAfter sodium channels have closed, some of the voltage-gated potassium channel still open, which causes the after hyperpolarized wave.
99Figure Graded potential and action potential. acting potentiallocal responseFigure Graded potential and action potential.
100Action Potential and its Origin Graded potentialDefinitionGraded potential( local response) are changes in membrane potential that are confined to a relatively small region of the plasma membrane.Characteristics① Electrotonic propagation.② Summation.③ Graded magnitude.
101Figure Electrotonic propagation of the graded potential.
103Figure Graded magnitude of the graded potential.
104Action Potential and its Origin Initiation of the action potentialAn action potential will not occur until the initial rise in membrane potential is great enough to create the positive feedback cycle of sodium channel, that is to say, to reach the threshold potential.
105Threshold potential Experiment Action potential Definition: -70ExperimentThreshold potentialAction potentialDefinition:The threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential.Threshold potential-55膜电位（mV）Graded potentialCharacteristics:① Create the positive feedback cycle of sodium channel.RP② From this moment on, the membrane events are independent of the initial stimulus.Stimulus
106Action Potential and its Origin Propagation of the action potentialMechanismThe potential difference between the depolarized areas of the membrane and adjacent resting membrane areas causes ions to flow, that is to say, the potential difference creates local currents, which causes the propagation of the action potential.Characteristics① Action potential propagate in both directions.② Action potentials are not conducted decrementally.③ The propagation follows the all-or-none principle.④ The velocity depends upon fiber diameter( larger diameter faster) and whether or not the fiber is myelinated( myelinated fiber faster).
107Figure Propagation of the action potential. Local currents+-+-+-+--+-+-++-+-+-+-+-+-+-Nerve fiberFigure Propagation of the action potential.
109Figure Contrast of propagation in nonmyelinated and myelinated axon (Saltatory Conduction).
110Action Potential and its Origin Contrast of action potential and graded potentialAction potentialGraded potentialMagnitudeLargeSmallSummationAll-or-nonepropagationElectrotonic propagationUnattenuated propagation
111Excitation and Excitability of Tissues Excitation and excitable cells and excitabilityExcitationExcitation is used to describe responses of a cell to stimuli. It has almost the same meanings as the action potential or the process that action potential produced.Excitable cells① Nerve cells.② Muscle cells.③ endocrine cells.④ immune cells.⑤ reproductive cells.
112Excitation and Excitability of Tissues Excitation and excitable cells and excitability.ExcitabilityThe ability to generate action potential is known as excitability.Excitability and threshold stimulusStimulus parameters: Intensity; duration; rate of change.Threshold intensity: The minimal intensity of stimulus to cause action potential of cells is called threshold intensity. This stimulus is called threshold stimulus.Subthreshold stimulus: the Stimulus is lower than threshold.
113Excitation and Excitability of Tissues Excitation and excitable cells and excitabilityExcitability and threshold stimulusSuprathreshold stimulus: the Stimulus is higher than threshold.Both threshold and suprathreshold stimulus cause action potential.Relationship between threshold potential and threshold stimulus.Threshold potential is the membrane potential to which a membrane must be depolarized to initiate an action potential.
114Excitation and Excitability of Tissues Excitation and excitable cells and excitabilityRelationship between threshold potential and threshold stimulus.Threshold stimulus are stimuli that are just strong enough to depolarize the membrane to the threshold potential.Threshold intensity or threshold stimulus is used as an index to evaluate the excitability.A series of excitability alteration after excitationAbsolute refractory period: During action potential , a second stimulus, no matter how strong, will not produce a second action potential.
115Excitation and Excitability of Tissues A series of excitability alteration after excitationRelative refractory period: During action potential , a second stimulus that is greater than usual can produce a second action potential.The refractory periods can:① Limit the number of action potentials.② contribute to the separation of these action potentials.③ determine the direction of action potential propagation.
116Figure The state of voltage-gated sodium ion channel. RestingOpenInactive
117Figure A series of excitability alteration after excitation.
118SMMURY ⑶ Membrane Potentials and Action Potentials Resting potential and its originAction potential and its originExcitation and excitability of tissues
119Contraction of Muscle Instructor: Zhu Su Hong Department of Physiology Jining medical collegeOffice: 0850 physiological sciences
120Functions of muscle contraction 1.Produce movement and Stabilize body positions2. Regulate organ volume3.Generate heat
121Characteristics of muscle tissue 1.Excitability – the ability to receive and respond to a stimulus (a neurotransmitter)2.Contractility – the ability to contract or shorten3.Extensibility – the ability to be extended or stretched4.Elasticity – the ability to recoil and resume the original resting length after being stretched
122Three Muscle TypesMuscle accounts for nearly half of the body’s mass - Muscles have the ability to change chemical energy (ATP) into mechanical energyThree types of Muscle Tissue – differ in structure location, means of activation and functionSkeletal MuscleCardiac MuscleSmooth Muscle
123General characteristics and functions of muscle skeletalstriatedvoluntaryProducing movement and heatcardiaclightly striatedinvoluntaryProviding power for blood circulationsmoothnon-striatedregulation of the internal enviroment
125How Can SKELETAL Muscles Contract ? 1.Being stimulated by a motor neuron2.Transmission of excitation at neuromuscular junction3.Excitation–contraction coupling4.Myofilament sliding
126How Can SKELETAL Muscles Contract ? 1.Being stimulated by a motor neuron2.Transmission of excitation at neuromuscular junction3.Excitation–contraction coupling4.Myofilament sliding
127Being stimulated by a motor neuron The Motor Unit
128How do STRIATED muscles contract? 1.Being stimulated by a motor neuron2.Transmission of excitation at neuromuscular junction3.Excitation–contraction coupling4.Myofilament sliding
129Transmission of excitation at neuromuscular junction 1. Physiologic Anatomy of the NeuromuscularJunction2. Major Processes of Excitation Transmission at Neuromuscular Junction3.Destruction of the Released Acetylcholine by ACE4.Disruction of Neuromuscular Signaling
130Transmission of excitation at neuromuscular junction 1. Physiologic Anatomy of the NeuromuscularJunction2. Major Processes of Excitation Transmission at Neuromuscular Junction3.Destruction of the Released Acetylcholine by ACE4.Disruction of Neuromuscular Signaling
132The Structure of Neuromuscular Junction Enlarge view of the neuromuscular junction
133The Structure of Neuromuscular Junction The neuromuscular junction be made of:prejunctional membrane=the axon terminaljunctional cleft=synaptic cleftpostjunctional membrane=the motor end plate
134Transmission of excitation at neuromuscular junction 1. Physiologic Anatomy of the NeuromuscularJunction2. Major Processes of Excitation Transmission at Neuromuscular Junction3.Destruction of the Released Acetylcholine by ACE4.Disruction of Neuromuscular Signaling
135Transmission of excitation at neuromuscular junction When a nerve impulse reaches the neuromuscularjunction:1.Voltage-regulated calcium channels in the axon membraneopen and allow Ca2+ to enter the axon2. Ca2+ inside the axon terminal causes some of the synapticvesicles to fuse with the axon membrane and release AChinto the synaptic cleft (exocytosis).3.ACh diffuses across the synaptic cleft and attaches to Achereceptors on the motor end-plate and Na+/K+ channel isopened when ACh binding to receptors.4. EPP is produced on the motor end-plate when Na+Diffusing into the cell.5.An action potential is generated adjacent the motor end-plate and propagated across the sarcolemma.
136Calcium channels open and Ca2+ diffusing into the cell
137Synaptic vesicles fuse with the axon membrane and release ACh into the synaptic cleft
138ACh attaching to receptors on the motor end-plate and Na+/K+ channels is open and Na+﹑K+ move cross the membrane
139Generation and Propagation of an Action Potential The sarcolemma, like other plasma membranes is polarized. There is a potential difference (voltage) across the membraneWhen Ach binds to its receptors on the motor end plate, chemically (ligand) gated ion channels in the receptors open and allow Na+ and K+ to move across the membrane, resulting in a transient change in membrane potential - DepolarizationEnd plate potential - a local depolarization that creates and spreads an action potential across the sarcolemma
140Generation and Propagation of an Action Potential The inside of the sarcolemma is negative relative to the outsideThe predominant extracellular ion is Na+ and the predominant intracellular ion is K+ (maintained by Na+- K+ ATPase)The difference in charge is the resting membrane potential (voltage)The sarcolemma is relatively impermeable to both ions
141Generation and Propagation of an Action Potential The axon terminal of a motor neuron releases ACh. ACh-receptor binding at the motor end plate results in production of an end plate potential as large number of Na+ diffuses into the cell.The resting membrane potential is decreased (local depolarization)。This is called EPP.↑ Na+ StimulusAlthough the EPP can not produce the action potential on the end-plate. because of lacking of voltage-gated sodium channels on the end-plate.
142Generation and Propagation of an Action Potential The EPP will travel in local current.The motor end plate potential may cause adjacent areas of the sarcolemma to become permeable to Na+ (voltage-gated sodium channels open) and adjacent areas of the sarcolemma depolarize as sodium follows its electrochemical gradient.So the action potential is generated and then travels over the sarcolemma.Once initiated, the action potential is unstoppable, and ultimately results in the contraction of a muscle.
144RepolarizationImmediately after the depolarization wave passes, the sarcolemma permeability changes.Na+ channels close and voltage-gated K+ channels open. K+ diffuses out of the cell, restoring the electrical polarity (but not the ionic conditions) of the resting state sarcolemma.
145Transmission of excitation at neuromuscular junction 1. Physiologic Anatomy of the NeuromuscularJunction2. Major Processes of Excitation Transmission at Neuromuscular Junction3.Destruction of the Released Acetylcholine by ACE4.Disruction of Neuromuscular Signaling
146The Ach once released into the synaptic cleft continues binding to its receptors.However at the same time most of ACh isdestroyed by ACE. ACh is hydrolyzed by ACEInto choline and acetate.So Ach terminates itfunction as a transmitter molecule. And theMembrane permeability returns to the resting state.The choline portion is taken up by theprejunctionary membrane for resynthesis of Ach andthe acetate diffuses away into the extracellular fluid.
147There is no Ach in the synaptic cleft, there is no action potential produced.So the skeletal muscle stops contracting.The skeletal muscle is stimulated onlyonce, the skeletal contracts only once!
149Summary Why? The muscle contraction is generated 1.The action potential travelles along the nerve fiber and arrives at the axon terminal2.Voltage-regulated Ca2+ channels open and Ca2+ enter into the axon3.Synaptic vesicles fuses with the axon terminal and release ACh into the cleft4.Binding ACh to receptors on the end-plate opens Na+/K+ channel5.The EPP is produced on the end-plate6.The action potential is generated and propagated along sarcolemmaWhy?The muscle contraction is generated
150Why the action potential on the sarcolemma lead to the muscle contraction?
151How Can SKELETAL Muscles Contract ? 1.Being stimulated by a motor neuron2.Transmission of excitation at neuromuscular junction3.Excitation–contraction coupling4.Myofilament sliding
152Muscles structure provides a key to understand the mechanism of striated muscle contraction!
153Physiologic Anatomy of Striated muscle a whole muscle consists ofa large number of musclefibers (cells) , plusconnective tissue wrappings,blood vessels, andnerve fibers.
154Skeletal Muscle – CT Sheaths Three connective tissue sheaths:Epimysium : surrounding the entire musclePerimysium : surrounding groups of muscle fibers (fascicles)Endomysium : surrounding each muscle fiber (cell)At each end of a muscle, the collagen fibers of the epimysium, perimysium, and endomysium come together to form a bundle of fibers called a tendon or a broad tendinous sheet called an aponeurosis.
155Muscle fibers are the principal part of the muscle.
156Microscopic Anatomy-Skeletal Muscle Fiber Each fiber is a long, cylindrical cell with multiple nuclei just beneath the sarcolemmaFibers are 10 to 100 m in diameter, and up to 30 cm longEach cell is a syncytium produced by fusion of embryonic cells
157Myofibrils account for about 80% of the cellular volume of a skeletal muscle fiber.They are the contractile elements of skeletal muscle fibers.
158Mycroscopic Anatomy-Myofibrils Within the myofibril, are thick and thin myofilaments. these myolfilaments are arranged in a regular pattern.The arrangement of myofibrils creates a series of repeating dark A bands and light I bands.
159What’ the dark band ? What’ the light band? How are the thick and thin filaments arranged into a regular pattern?What’ the dark band ?What’ the light band?
160One unit of this repeating pattern is known as a sarcomere. The thick and thin filaments in each myofibril are arranged in a repeating regular pattern along the length of the myofibril.One unit of this repeating pattern is known as a sarcomere.
161A band extend the entire length of thick filaments. The thick filaments are located in the middle of each sarcomere and there orderly parallel arrangement produces a wide ,dark band called the A band .sarcomereA band extend the entire length of thick filaments.
162Each sarcomere contains two sets of thin filaments.One at each end.One end of each thin filament is anchored to anetwork of interconnection proteins called the Zlines.While the other end overlaps a portion of thethick filaments.Between the two successive Z line is a sarcomere.Thin filaments from the two adjacent sarcomeresare anchored to the two sides of each Z line.
164Those portions of the thin filaments that do not overlap the thick filament appears light.We call those the I band.The I band lies between the end of A bands of two adjacent sarcomeres and contains the two adjacent thin filaments. The I band is anchored by the Z line.
165In the central of the H band is a dark line called the M line. The edges of the A band are darker in appearance than the centre region. The central lighter region of the A band is called the the H band.The H band thus contains only thick filaments that are not overlapped by thin filaments.sarcomereIn the central of the H band is a dark line called the M line.
166The M line is produced by proteins located at the centre of the thick filaments in a sarcomere. The M lines serve to anchor the thick filaments,helping them stay together during contraction.sarcomere
169T Tubules – (transverse) T tubules at each A band - I band junction are continuous with the sarcolemma. The lumen of the tubule is continuous with the extracellular space.Conduct electrical impulses to the muscle (every sarcomere) - signals for the release of Ca2+ from adjacent terminal cisternaeT tubule
170Sarcoplasmic Reticulum (SR) SR - an elaborate, smooth ER that surrounds each myofibril. It is composed of two major parts.(1) Long longitudinal tubules ;(2) Terminal Cisterns.SR regulates intracellular Ca2+triadtriadTerminal Cistern
171Triad – 2 terminal cisternae and 1 T tubule T tubules and SR provide tightly linked signals for muscle contractionT tubule proteins act as voltage sensorsSR proteins are receptors that regulate Ca2+ release from the SR cistern
172In order to comprehend the filament sliding we also ought tostudy the structure of the filaments.
173Thick FilamentsThe thick filaments are composed almost entirely of the contractile protein myosin.
174Thin FilamentsThin filaments (F actin) are mostly composed of the protein actin. The regulatory protein- tropomyosin and troponin are bound to actin .On each actin molecular ,there is a myosin binding site where a cross-bridge can attach.
176Myofilament Sliding Theory In the relaxed state, actin and myosin filaments do not fully overlap.With stimulation by the nervous system, myosin heads bind to actin and pull the thin filaments.Actin filaments then slide past the myosin filaments so that the actin and myosin filaments overlap to a greater degree (the actin filaments are moved toward the center of the sarcomere, Z lines become closer)
177Sliding Filament Model of Contraction Relaxed State
178Sliding Filament Model of Contraction Partially Contracted
179Sliding Filament Model of Contraction Fully Contracted
180Myofilament Sliding theory During shortening,the sarcomere is shortened, but there is no change in the length of either the thick or thin filaments.During shortening，there is only change in the length of light band and there is no change of dark band.
181One stroke of a cross–bridge produces only a very small movement One stroke of a cross–bridge produces only a very small movement .As long as a muscle fiber remains activated , each cross-bridge repeats its swiveling many times .It will lead to large displacements of the filaments.
182When the filaments slide, the cross-bridge will undergo four different states .We call it cross-bridge cycle.It is the integral process that the actin andmyosin filaments slide.
183Cross-bridge cycle Each cross-bridge cycle consists of four steps : 1.Attaching of myosin cross-bridge to the actin ofthin filament.2.Movement of the cross-bridge ,producingtension in the thin filament .3.Detachment of the cross-bridge from the thinfilament.4.Energizing the cross-bridge so that it can againattach to a thin filament and repeats the cycle.
185Cross-bridge cycle Step:2 Movement of cross-bridge. A ﹒M ﹒ADP﹒Pi A ﹒M + ADP + Pi
186During the cross-bridge movement myosin is bound to actin very firmly During the cross-bridge movement myosin is bound to actin very firmly. This linkage must be broken in order to allow the cross-bridge to attach to another portion of the actin filament, as to make the thin filaments slide toward the center of the sarcomere.
187Cross-bridge cycle Step:3 Dissociation of cross-bridge from actin. A ﹒M + ATP A + M ﹒ATPIn this step,ATP is not split.Here ATP is not acting as an energy source but only as an allosteric modulator of the myosin.So it can weaken the binding of myosin to actin.
188Cross-bridge cycle Step:4 ATP hydrolysis A + M ﹒ATP A + M ﹒ADP﹒Pi Following the dissociation of myosin from actin ,the ATP bound to myosin is hydrolysis, thereby reforming the energized state of myosin with ADP and Pi binding to the cross-bridge again.
190The cross-bridge cycle repeats as long as ATP is available and the Ca2+ level near the thin filament ishigh. We can see that the Ca2+ plays an importantrole in the cross-bridge cycle, it can start and stop thefilaments sliding.Why does the high level of Ca2+ in the cytoplasminitiate the energized cross-bridge attaching to actin?Let us study the Ca2+ and the contraction mechanism.
191Thin Filament Regulatory Proteins Two Tropomyosin strands spiral around the actin filament and block the myosin-binding sites in a relaxed muscle fiberTroponin is a three-polypeptide complex: TnI - Inhibitory subunit that binds to actin TnT - binds to Tropomyosin TnC - binds to Calcium ions
192Ca2+ and the Contraction Mechanism At low intracellular Ca2+, tropomyosin blocks the binding sites on actin and myosin cannot attach – this is the relaxed state.
193Ca2+ and the Contraction Mechanism As Ca2+ levels rise, ions bind to troponin regulatory sites.Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site.
194Ca2+ and the Contraction Mechanism Calcium-activated troponin undergoes a conformational change. This change moves tropomyosin away from actin’s binding sites.
195Ca2+ and the Contraction Mechanism Displacement of the tropomyosin allows the myosin head to bind to the actin and the cross-bridge cycle of contraction begins
196How can the high level of Ca2+ in the cytoplasm be available? The change of Calcium level is controlled by electrical events in the muscle plasma membrane.This is Excitation-contraction coupling.
197Excitation-Contraction Coupling 1.Definition: E-C Coupling is the sequence of events linking the transmission of an action potential along the sarcolemma to muscle contraction (the sliding of myofilaments).triad2.position: at the triad3. the process
198The process of Excitation-Contraction Coupling The action potential is propagated along (across) the sarcolemma and travels through the T tubulesAt the triads, the action potential causes voltage sensitive T tubule proteins to change shape.This change, in turn, causes the SR proteins of the terminal cisterns to change shape, Ca2+ channels are opened and Ca2+ is released into the sarcoplasm from the terminal cisterns.(where the myofilaments are)
199The process of Excitation-Contraction Coupling Some of the Ca2+ binds to troponin, troponin changes shape and causes tropomyosin to move which exposes the active binding sites on actin.Myosin heads can now alternately attach and detach, pulling the actin filaments toward the center of the sarcomere. (ATP hydrolysis is necessary)
200The process of Excitation-Contraction Coupling The short calcium influx ends (30 ms after the action potential ends) and Ca2+ levels fall. An ATP-dependent Ca2+ pump is continually moving Ca2+ back into the SR.Tropomyosin blockage of the actin binding sites is reestablished as Ca2+ levels drop. Cross-bridge activity ends and relaxation occurs
201Excitation-Contraction Coupling Action potential in the T-tubules causes the release of Ca2+ from the SR. This process is known as E-C Coupling.
202Summary: how can the skeletal muscle contract ?
203Performance of Contraction The muscular performance of contractionincludes:1.the muscular tension2.the muscular shortening3.the velocity of change of the tensionand shortening during the contraction
204the muscular tension （1）Definition: the force exerted on an object by a contracting muscle is known as musculartention.It must be distinguished from the load.Load: the force exerted on the muscle by anobject (usually its weight).（2）Isotonic contraction: a muscle contraction issaid to be isotonic contraction when it shortswith the tension remain constant.
205the muscular shortening Isometric contractionDefinition: when a muscle develops tension but doesnot shorten(or lengthen), the contraction is said to beisometric contraction.Such contractions occur when the muscle supports aload in a constant position or attempts to move anotherwise supported load that is greater than thetension developed by the muscle.For example holding a dumbbell at a constant positionrequires muscle contraction but not muscle shortening.
206be influenced by (2) afterload (3) contractility The performance of contraction canbe influenced by(1) preload(2) afterload(3) contractility(4) summation of the contractions
207Preload (Length-force relationship) (1)Definition: the force on the muscle prior to contraction.It sets the initial length of the muscle.At any given length ,if the muscle is stimulated to cause isometric contraction,it will develop an additional amount of tension(active tension), which is a function of the initial fiber length. while the passive tension is directly related to the extent to which a muscle is stretched.(2) Effect of preload on force of contraction(Length-force relationship)
208Length-force relationship As the preload increases, the resting length of themuscle increases and the ability of the muscle todevelop tension and shorten increases, with limits.Therefore ,there is an optimal length at which peaktension will be developed. At lengths shorter orlonger than this, developed tension (active)decreased. The relationship can be partially explained in terms of the filaments sliding mechanism.
209Length-force relationship DLength-tension diagram for a single sarcomere shows maximum strength of contraction when the sarcomere is 2.0 to 2.2 micromeres in length.At the upper right are shown the relative positions of the actin and myosin filaments at different sarcomere length from point A to point D.
210Length-force relationship Stretching a fiber to about the length of D point, pulls the filaments apart so that there is no overlap.At this point there can be no cross-bridge binding to actin so no development of tension.Between D and C more and more filaments overlap, and the tension is produced in proportion to the increased number of cross-bridges in the overlap region At point B and C all the cross-bridges can bind to the actin filaments, thereby producing maximal tension. At lengths less than B,the tension declines.D
211Afterload (1)Definition: the afterload is the force on the muscle during the contraction.The afterload determines the work that themuscle must do.(2) Effect of Afterload on Muscle Contraction(Force-Velocity Relationship)In general ,the lighter the afterload, the faster themuscle shortens and the more it shortens. As theafterload is increased, the velocity of shorteningand the amount of shortening decrease.
212Force-Velocity Relationship The shortening velocity is maximal when there is no load and is zero when the load is equal to the maximal isometric tension.If the afterload is greater than the muscle can lift, the muscle develops tension without shortening external.Relation of load to velocity of contraction in a skeletal muscle
213ContractilityThe muscle contractility refers to the inherent strength of the muscle and is independence of loads.It is determined by calcium levels in the sarcoplasm and myosin ATPase activity.
214Force summation Summation occurs in two ways: (1)by Increasing the number of motor unitswhich is called Multiple Fiber Summation.(2)By increasing the frequency ofstimulation which is called Frequencysummation.
215A twitch1.Definition: the mechanical response of a single contraction to a single action potential is known as a twitch.2.There are there phases(1) latent period(2) period of contraction(3) period of relaxation
216Three phases of muscle contraction Following the action potential, there is an interval ofa few milliseconds before the muscle begins tocontract, known as the latent period.The time from the beginning of tension developmentat the end of the latent period to the peak tension isthe contraction period.The relaxation period follows the contraction periodand is the result of Ca2+ ion concentration returningto normal levels。
217Three phases of muscle contraction The curve of the twitch of a skeletal muscle
218Since a single action potential in a skeletal muscle fiber lasts 1 to 2ms but the twitch maylast 100ms,it is possible for a second actionpotential to be initiated during the period ofcontraction or relaxation.The increase in muscle tension from successiveaction potentials occurring during the phase ofmechanical activity is known as summation.A maintained contraction in response to repetitivestimulation is known as tetanus.
220Incomplete tetanus1.Definition: Each new contraction occurs before the previous one is over (The second contraction is added partially to the first).2.Characteristics: the relaxation phase is becoming shorter and shorter.twitchIncomplete tetanuscomplete tetanus
221Complete tetanus 1.Definition: The successive contraction are so close that they fuse together and appears to becompletely smooth and continuous.2.Characteristics:the relaxation phase is disappear.twitchIncomplete tetanuscomplete tetanus