1. M1 Nerve/Muscle Physiology Exam Review 9/1/04 Stacy Trent and Joe Walsh

2. Test Details: 1) Approx. 3 questions per lecture 2) 1.2 minutes per question 3) Department practice exam on Blackboard 4) TLEs on M1 website (go to: “Class Materials” then “Physiology”)

3. Membranes

4.  Fluid Mosaic Model Phospholipid bilayer with proteins and cholesterol embedded within bilayer. Phospholipid bilayer with proteins and cholesterol embedded within bilayer. Cholesterol makes bilayer stiffer or more viscous!! Cholesterol makes bilayer stiffer or more viscous!! Membrane composition depends on function (ie. More lipid in Schwann cells and more protein in mitochondria). Membrane composition depends on function (ie. More lipid in Schwann cells and more protein in mitochondria).  Intrinsic/Integral vs. Extrinisic/Peripheral Proteins Intrinsic proteins span the entire membrane and contain hydrophillic ends and a hydrophobic core, often serving as transporters. Intrinsic proteins span the entire membrane and contain hydrophillic ends and a hydrophobic core, often serving as transporters. Extrinsic proteins are present on one side of the bilayer or the other and are anchored by electrostatic interactions. Extrinsic proteins are present on one side of the bilayer or the other and are anchored by electrostatic interactions. Glycolipids can be conjugated with either an intrinsic or extrinsic protein and serve as a surface marker for the cell. Glycolipids can be conjugated with either an intrinsic or extrinsic protein and serve as a surface marker for the cell.

5. Transport 1) Simple Diffusion - small, nonpolar > large, polar 2) Osmosis - water follows solute - water follows solute 3) Facilitated Diffusion - not energy dependent transport of solute down its concentration gradient - not energy dependent transport of solute down its concentration gradient 4) Active Transport - energy dependent transport of solute against its concentration gradient - energy dependent transport of solute against its concentration gradient Note: All transport mechanisms exhibit saturation kinetics, chemical specificity and competitive inhibition. When the [substrate] increases, the transportation rate increases until transport mechanism becomes saturated.

6. Transport

7. Diffusion  Diffusion is driven by concentration gradients.  Fick’s 1st Law of Diffusion: Use to calculate Rate of Diffusion Use to calculate Rate of Diffusion Note: ∆C = C 1 -C 2 where C 1 = target compartment Note: ∆C = C 1 -C 2 where C 1 = target compartment  Stokes-Einstein Equation: Use to calculate Diffusion Coefficient Use to calculate Diffusion Coefficient  Partition Coefficient (  ) Expresses relative Lipid Solubility Expresses relative Lipid Solubility 0 (lipid insoluble)  1 (completely lipid soluble) 0 (lipid insoluble)  1 (completely lipid soluble)

8. Which factors allow fast diffusion? 1. Lipid solubility (  ) - the more lipid soluble, the faster the diffusion. 2. ∆C - the greater the change in concentration, the faster the diffusion. 3. Membrane thickness - the thinner the membrane, the faster the diffusion. 4. Viscosity of membrane - the less viscous the membrane, the faster the diffusion. 5. Radius of molecule - the smaller the radius of the molecule, the faster the diffusion.

9. Osmosis  Van’t Hoff’s Law: π=RT(  iC) o Use to calculate osmotic pressure o π = pressure required to oppose the movement of water from an area of high [H 2 O] (low osmolarity) to an area of low [H 2 O] (high osmolarity).  Osmotic Flow Rate o V w =L  ∆π o Use to calculate the osmotic flow rate of water when the membrane is permeable to both water and solute. o  = reflection coefficient (0-1) - a high reflection coefficient reflects a solute that does NOT permeate the membrane well.

10. Hypertonic vs. Hypotonic Solutions  Hypotonic solutions have a lower osmolarity than cellular osmolarity (0.3 osm) and thus the cell will swell when placed in a hypotonic solution. “Cell will swell in hypOtonic solution” “Cell will swell in hypOtonic solution”  Hypertonic solutions have a higher osmolarity than cellular osmolarity and thus the cell will shrink when placed in a hypertonic solution.

11. Facilitated Diffusion  Helps larger, less soluble molecules cross the membrane  Dependent on concentration gradient  No Energy Needed!

12. Active Transport

13.  Against concentration gradient  Requires Energy (ATP)  Primary Active Transport Transporter directly breaks down an energy molecules (mostly ATP…Na + /K + pump) Transporter directly breaks down an energy molecules (mostly ATP…Na + /K + pump)  Secondary Active Transport Transporter is indirectly dependent on energy expenditure from another transporter Transporter is indirectly dependent on energy expenditure from another transporter ex. Na/glucose co-transporter fueled by Na + /K + pump ex. Na/glucose co-transporter fueled by Na + /K + pump NOTE: Na + /K + pump = PumpKin (Pump K + in)NOTE: Na + /K + pump = PumpKin (Pump K + in)

14.  Gated Channels Utilize gradient: high to low [ ] Utilize gradient: high to low [ ] Ligand Gated Channels - passive diffusion through a channel opened through ligand binding (hormone or neurotransmitters)Ligand Gated Channels - passive diffusion through a channel opened through ligand binding (hormone or neurotransmitters) Voltage Gated Channels - passive diffusion through a channel opened by changes in the membrane potentialVoltage Gated Channels - passive diffusion through a channel opened by changes in the membrane potential  Vesicle Mediated Transport Requires Energy!! Requires Energy!! Endocytosis - into cell Endocytosis - into cell Exocytosis - out of cell Exocytosis - out of cell

15. Membrane Potentials  Results because of an unequal distribution of charge across a membrane  Two equations you need to know: 1) Nernst Equation 2) Goldman’s Equation

16.  Nernst Equation: (Don’t forget about “z”…valence of ion) - Use to calculate the membrane potential of an ion at equilibrium - Represents the electrical potential necessary to maintain a certain concentration gradient of a permeable solute.

17.  Goldman’s Equation Used to calculate overall membrane potential when multiple ions are involved. Used to calculate overall membrane potential when multiple ions are involved. Incorporates permeability of each ion. Incorporates permeability of each ion. Permeability of K + > Na + > Cl - … thus.. Permeability of K + > Na + > Cl - … thus.. K+ drives Resting Membrane Potential

18. Neurotransmitters  Acetylcholine (ACh) Somatic NS Somatic NS At neuromuscular junctionAt neuromuscular junction Autonomic NS Autonomic NS Preganglionic PNS and SNS neuronsPreganglionic PNS and SNS neurons Postganglionic PNSPostganglionic PNS  Norepinephrine ANS- postganglionic SNS neurons ANS- postganglionic SNS neurons  GABA Inhibitory neurotransmitter of brain Inhibitory neurotransmitter of brain  Glutamate Excitatory neurotransmitter of brain Excitatory neurotransmitter of brain

19. Receptors  Ionotropic - binding of NT opens ion channel nACh receptors - Na+ and K+ channels nACh receptors - Na+ and K+ channels At neuromuscular junction and autonomic ganglionAt neuromuscular junction and autonomic ganglion GABA receptors - ligand gated Cl- channels GABA receptors - ligand gated Cl- channels Glutamate receptors Glutamate receptors Non-NMDA - ligand gated Na+ and K+ channelsNon-NMDA - ligand gated Na+ and K+ channels NMDANMDA Must bind glycine to be active Must bind glycine to be active Ligand gated Na, K and Ca channels blocked by Mg at rest Ligand gated Na, K and Ca channels blocked by Mg at rest  Metabotropic - binding of NT generates a 2nd messenger which opens an ion channel Binding activates G- protein which activates and enzyme serving as a 2nd messenger mACh receptors At PNS effector organs  1,  2,  1,  2, and  3 At SNS effector organs

20. SNS Receptors   1 - contraction (sphincters)   2 - decreases sections (salivary glands)   1 - heart (excitatory) and kidney   2 - lungs, pupil (relaxation) Mnemonic: 1 , 2 lungs

21. Agonists and Antagonists  Pro-PNS Effects Neostigmine - Inhibits Acetylcholinesterase prolonging ACh activity Neostigmine - Inhibits Acetylcholinesterase prolonging ACh activity Propanolol -  antagonist Propanolol -  antagonist  Pro-SNS Effects Isoprotenerol -  agonist Isoprotenerol -  agonist Belladonna and Atropine - mACh antagonist Belladonna and Atropine - mACh antagonist  Anti-ANS (both PNS and SNS) Hexamethonium - nACh antagonist (ganglia) Hexamethonium - nACh antagonist (ganglia)  Anti-Skeletal Muscle Contraction Curare - nACh antagonist (NMJ) Curare - nACh antagonist (NMJ)

22. Action Potentials (AP’s)  AP’s are the result of time and voltage dependent changes in ionic permeability of excitable cells (i.e. neurons).  Na + and K + channels that generate AP’s are only found at the axon hillock. Any other depolarization in a neuron is called a receptor potential.  AP’s are ALL-OR-NOTHING events. A stronger stimulus only increases the frequency of firing.

23. Phases of Action Potentials 1. Slow depolarization to threshold 2. Rapid depolarization due to opening of voltage dependent Na + channels leading to Na + influx (Hodgkin Cycle!) 3. Repolarization due to increased K + conductance leading to K + efflux 4. Hyperpolarization (refractory period) 5. Resting membrane potential

24. Refractory Periods  Absolute Refractory Period - due to time dependence of Na + channel No amount of inward current will generate another AP Due to the Na + inactivation gate which is slow to close when triggered at threshold  Relative Refractory Period Need an excess of current to generate an AP because the Na+ channels are still inactivated until the end of repolarization phase

25. Velocity of Conduction of AP  Velocity increases with increased diameter of axon.  Velocity increases when membrane resistance increases (myelination!)

26. Synaptic Transmission  Presynaptic Membrane: AP  Ca +2 channels opening  Ca +2 influx  synaptic vesicle fusion  release of NT’s AP  Ca +2 channels opening  Ca +2 influx  synaptic vesicle fusion  release of NT’s  Post-synaptic membrane: Neurotransmitter binds to postsynaptic neuron or muscle leading to increased conductance of Na+ and K+ causing a generator or action potential. Neurotransmitter binds to postsynaptic neuron or muscle leading to increased conductance of Na+ and K+ causing a generator or action potential. http://mcb.berkeley.edu/courses/mcb136/topic/Tissue_Cells_Membranes/SlideSet3/AP%20review_files/slide0012_image012.gif

27. Response of Post-Synaptic Cell  Response may be inhibitory or excitatory depending on the nature of postsynaptic cell (NOT Neurotransmitter!!)  Temporal or Spatial Summation Temporal - multiple signals from 1 axon firing in rapid succession such that successive inputs add to the still- existent present inputs. Temporal - multiple signals from 1 axon firing in rapid succession such that successive inputs add to the still- existent present inputs. Spatial - multiple signals from different axons occurring simultaneously. Spatial - multiple signals from different axons occurring simultaneously.  Repetitive Stimulations Facilitation - successive APs cause postsynaptic membrane potential to grow more and more intense in amplification Facilitation - successive APs cause postsynaptic membrane potential to grow more and more intense in amplification Post-tetanic Potentiation - after repetitive firing, Ca +2 channels are synchronized resulting in a more amplified EPSP following tetanus Post-tetanic Potentiation - after repetitive firing, Ca +2 channels are synchronized resulting in a more amplified EPSP following tetanus Synaptic Fatigue - delay in response after synapse following prolonged tetanus (NTs have to be re-packaged) Synaptic Fatigue - delay in response after synapse following prolonged tetanus (NTs have to be re-packaged)

28. Generator vs. Action Potentials  Generator Potentials Subthreshold Subthreshold Graded Graded Intensity of signal = larger response Intensity of signal = larger response Decremental conductance Decremental conductance Longer length constant = less decrementLonger length constant = less decrement Larger nerves = longer length constantLarger nerves = longer length constant  Action Potentials Over threshold All or Nothing!!! Intensity of signal = more frequent Aps No decrement in signal

29. Autonomic vs. Somatic NS  Somatic NS Acts on skeletal muscles Acts on skeletal muscles 1 neuron 1 neuron ACh  nACh (motor end plate) ACh  nACh (motor end plate) Controlled by voluntary thought (motor cortex) Controlled by voluntary thought (motor cortex)  Autonomic NS Acts on smooth muscle, glands, cardiac muscle 2 neurons: post and preganglionic PreG: ACh  nACh Post G: PNS: ACh  mACh SNS: NE   or  Controlled by hypothalamus (involuntary) Associated w/ limbic system leads to emotionally linked response Ablation (can’t respond to changes)

30. Autonomic NS  Sympathetic Cell bodies of postganglionic nerves are in ganglia near spinal cord Cell bodies of postganglionic nerves are in ganglia near spinal cord Diffuse control (1:10 ratio of pre to postG fibers) Diffuse control (1:10 ratio of pre to postG fibers) Short preganglionic nerves (ACh  nACh receptors) Short preganglionic nerves (ACh  nACh receptors) Long post ganglionic nerves (NE   1,  2,  1 and  2) Long post ganglionic nerves (NE   1,  2,  1 and  2)  Parasympathetic Cell bodies of postganglionic nerves are in ganglia near organ Precise control (1:3 ratio of pre to postG fibers) Long preganglionic nerves (ACh  nACh receptors) Short postganglionic nerves (ACh  mACh receptors)

31. SNS vs. PNS

32.  SNS = fight or flight Dilates pupils Dilates pupils Opens airways Opens airways Increases heart rate and BP Increases heart rate and BP Increases blood flow to heart, brain and skeletal muscle Increases blood flow to heart, brain and skeletal muscle Inhibits digestion Inhibits digestion Piloerection Piloerection Gluconeogenesis and glycogenolysis (makes glucose available) Gluconeogenesis and glycogenolysis (makes glucose available)  PNS = rest and digest Constricts pupils Restricts airways Decreases heart rate and BP Promotes digestion Increases blood flow to gut Increase saliva Glyconeogenesis (stores glucose as glycogen)

33. SNS vs. PNS  Salivary Secretions: SNS:  salivary amylase production SNS:  salivary amylase production PNS:  watery saliva PNS:  watery saliva  Defecation SNS:  motility of colon until “appropriate time” SNS:  motility of colon until “appropriate time” PNS:  motility of colon leads to expulsion of stool PNS:  motility of colon leads to expulsion of stool  Urination SNS: Relaxation of bladder to allow for fill-up SNS: Relaxation of bladder to allow for fill-up PNS: Contraction of bladder PNS: Contraction of bladder  Erection SNS: Ejaculation and psychogenic erections SNS: Ejaculation and psychogenic erections PNS: Erection (ACh  NO release  vasodilation) PNS: Erection (ACh  NO release  vasodilation)

34. Muscle

35. Skeletal Muscle  Controlled by Somatic NS  Skeletal muscle specific terms: Neuromuscular junction Neuromuscular junction Motor endplate – skeletal muscle on the receiving end of nm junction Motor endplate – skeletal muscle on the receiving end of nm junction End Plate Potential (EPP) – generator potential of skeletal muscle End Plate Potential (EPP) – generator potential of skeletal muscle  ACh release is quantal (miniature end plate potential = 0.4 mV)

36. Organization and Structure of Muscle

37. Classification of Muscle Striated Muscle Smooth Muscle Multi-Unit Single-Unit Cardiac Skeletal Functional Syncytium Automaticity Motor Unit Composition Motor Nerve Required

38. Connective Tissue (Know this!)  Epimysium surrounds entire muscle surrounds entire muscle  Perimysium separates muscle into bundles of muscle fibers (fascicles) separates muscle into bundles of muscle fibers (fascicles) contains blood vessels contains blood vessels  Endomysium separates muscle fascicles into individual muscle cells (myofibers) separates muscle fascicles into individual muscle cells (myofibers) contains capillaries contains capillaries Epimysium, perimysium, and endomysium all come together at the ends of muscles to form TENDONS

39. Anatomy of a Muscle c Nerves and blood vessels are embedded in connective tissue. The major connective tissue components are collagen and elastin. Muscles are attached to bones by tendons at their origin and insertion.

40. Muscle Growth During Development Activated by injury or trauma Cell Division (Hyperplasia) Cell Fusion Cell Growth (Hypertrophy) Satellite Cell (quiescent) Re-Enter the Cell Cycle Myoblasts Myotubes Myofibers

41. The Sarcomere Basic Contractile Unit in Muscle M line

42. Myofilament Arrangements ½ I A When muscle contracts, the sarcomere shortens. The I band and H Zone also shorten. But the length of the A band remains the same. A cross-section through the A Band/I Band overlap shows the hexagonal array of thick and thin myofilaments

43. The Thick Myofilament The thick myofilaments are composed of myosin molecules arranged in an end to end fashion at the M-line. Each myosin is composed of two myosin heavy chain subunits and two pair of myosin light chains. Myosin Light Chains MHC – 220,000 Daltons MLC – 15 – 20,000 Daltons

44. Thin myofilaments Actin core Actin core Tropomyosin Tropomyosin Filamentous protein blocks myosin binding site on actinFilamentous protein blocks myosin binding site on actin Troponin Troponin T – attaches troponin complex to tropomyosinT – attaches troponin complex to tropomyosin I – along with tropomyosin inhibits myosin binding site on actinI – along with tropomyosin inhibits myosin binding site on actin C – binds free intracellular calcium to produce a conformational change in tropomyosinC – binds free intracellular calcium to produce a conformational change in tropomyosin

45. Other Structural Proteins  Titin keeps thick myofilaments centered in sarcomere keeps thick myofilaments centered in sarcomere extends from M line to Z line, largest MW protein known extends from M line to Z line, largest MW protein known  Nebulin determines length of thin myofilaments, “molecular ruler” determines length of thin myofilaments, “molecular ruler”  Alpha Actinin – anchors thin myofilaments to the Z-line  Beta Actinin – determines length of thin filaments  Myomesin – binds titin, aligns thick filaments into hexagonal array  Desmin – cytoskeletal protein, connects adjacent sarcomeres  C-, H-, and X- proteins – form rings around thick filaments, maintains thick filament structure during contraction  Cap-Z and tropomodulin – associated with opposite ends of growing thin filaments, regulates length  Dystrophin – anchors actin filaments to sarcolemma, defective in MD  Myotilin – interacts with alpha actinin and Z-lines, sarcomeric organization

46. Nerve – Muscle Relation

47. Some definitions…  Motor Unit Composed of an alpha motorneuron and all the myofibers innervated by that neuron Composed of an alpha motorneuron and all the myofibers innervated by that neuron  Motor Endplate The region of the myofiber directly under the terminal axon branches The region of the myofiber directly under the terminal axon branches  Neuromuscular junction Where the axon terminal and the motor endplate meet Where the axon terminal and the motor endplate meet

48. Size Principle of Motor Unit Recruitment Input from CNS Corticospinal Tract Small Cell Body few myofibers easily recruited Large Cell Body Type I Type II Recruited First Finesse Contractions Recruited Last Forceful Contractions Spinal chord Two different motor units within the same myofiber

49. Acetylcholine receptor

50. T-tubules are aligned w/ ends of A band(near myosin heads).

51. Excitation-Contraction Coupling Resting Muscle DHP Receptor RyR Receptor Ca ++ Calsequestrin Ca ++ + + _ _ ATP No at resting membrane potential SR-Ca ++ ATPase

52. Excitation-Contraction Coupling Contracting Muscle DHP Receptor RyR Receptor Ca ++ Calsequestrin Ca ++ + + ++ ATP Depolarized Crossbridge Formation Sarcomeric Shortening Ca++ SR-Ca ++ ATPase

53. Excitation-Contraction Coupling Relaxing Muscle DHP Receptor RyR Receptor Ca ++ Calsequestrin Ca ++ + + _ _ ADP + Pi No at resting membrane potential Ca++ SR-Ca ++ ATPase Tension is longer than electrical or biochemical events

54. Steps in excitation-contraction coupling: 1)Action Potential 2)Depolarization of the T-Tubules - Causes conformational change in the DHPR - opens Ca 2+ channels(Ryr) on sacroplasmic reticulum 3)Ca 2+ released from SR into ICF 4)Ca 2+ binds to Troponin C cooperatively - causes conformational change 5)Tropomyosin is out of way 6)Cross-bridge cycling 7)Relaxation via Ca 2+ ATPase

55. Crossbridge detachment ATP ADP + P i A M A M ATP A M ADP P i A + M ADP P i (Charged Intermediate) Relaxed state Rigor mortis if no ATP Crossbridge energized Crossbridge attachment Crossbrige Motion Ca 2 Actin-Myosin Binding Sites 3 The Crossbridge Cycle

56. Crossbridge Motion Changes in the conformation of the hinge region of the myosin molecule allow for swivel motion of the crossbridges that produces sarcomeric shortening. Features of the Crossbridge Cycle 1)CB cycle is repetitive 2)CB cycle is asynchronous 3)Tension is proportional to CB number 4)Velocity is proportional to cycle rate 5)Velocity is inversely proportional to load

57. Sliding Filament Theory  Describes the mechanism of muscle contraction  Free energy from cleavage of Mg*ATP induces a bend in myosin head from a 90 to 45 degree angle  Actin filaments slide toward the H zone, pulling the Z lines inward  Sarcomere shortens and muscle contracts  This happens in a wave - not synchronous for each sarcomere

58. Sample Question #1 Lengths at rest: A band = 1.5  m I band = 1.0  m H zone = 0.7  m What is the length of the… a) sarcomere? b) thin filament? c) overlap?

59. Sample Question #1 Lengths at rest: A band = 1.5  m I band = 1.0  m H zone = 0.7  m What is the length of the… a) sarcomere? 1.5 + 1.0 = 2.5  m b) thin filament? (2.5 – 0.7) / 2 = 0.9  m c) overlap? 1.5 – 0.7 = 0.8  m

60. Sample Question #2 Lengths at rest: A band = 1.5  m I band = 1.0  m H zone = 0.7  m Sarcomere = 2.5  m During contraction, the muscle shortens by 20%. What is the length of the… a) sarcomere? b) thick filament? c) I band? d) H zone? e) overlap?

61. Sample Question #2 Lengths at rest: A band = 1.5  m I band = 1.0  m H zone = 0.7  m Sarcomere = 2.5  m During contraction, the muscle shortens by 20%. What is the length of the… a) sarcomere? 2.5 – 0.5 = 2.0  m b) thick filament?1.5  m (no change!) c) I band? 2.0 – 1.5 = 0.5  m d) H zone?2.0 – [(2) x (0.9)] = 0.2  m e) overlap? 1.5 – 0.2 = 1.3  m

62. Length – Tension Relationship  Generation of tension in a muscle depends on its initial length  Maximal tension can be developed at a sarcomere’s optimal length, usually its resting length  At the optimal length, a maximum number of cross- bridge sites are accessible to the actin molecules for binding and bending  When a muscle is passively stretched, the thin filaments are pulled out and there are less actin sites available for cross-bridge binding, decreasing tension  When a muscle is shorter than its optimal length, tension decreases because the thin filaments overlap and the thick filaments become forced against the Z-lines

63. Length vs. Tension AT OPTIMAL LENGTH - maximum # of crossbridges > OPTIMAL LENGTH - thin filaments pulled away and less room on actin for binding = less tension < OPTIMAL LENGTH - thin filaments overlap, thick filaments run into Z lines = less tension

64. Active State  Describes criteria which must be met for contraction to occur: a) binding of calcium to troponin C b) cross-bridge formation c) ATP splitting d) cross-bridge motion Twitch force Ca-troponin complex Myoplasmic [Ca] Action potential

65. Elastic and Contractile Components Contractile Component Parallel Elastic Component Series Elastic Component 1) Contractile Component: Responsible for Active Tension(proportional to # of crossbridges that cycle) 2)Parallel Elastic Component: Responsible for Passive Tension 3)Series Elastic Component: Must be stretched in order to develop active tension

66. Modulation of Muscle Contraction

67. Summation  Muscle force can be modulated by the frequency of stimulation  Depends on active state and refractory period  Skeletal muscle exhibits a long active state and a short refractory period  Allows a second action potential long before the initial twitch response is complete  Subsequent twitches build upon the one before, ultimately achieving a tetanus state

68. Summation of Twitches The force of muscle contraction can be increased by increasing the frequency of nerve stimulation. The key is the difference in the time course for the action potential, calcium transient, and mechanical response.

69. Tetanus and Fatigue 1/sec 5/sec 10/sec50/sec Stimulation at low frequencies produces summation of twitches and tetanus. However, when stimulation frequency reaches a rate rapid enough to produce a complete tetanus, fatigue will develop. Fatigue in tetany is due to fast twitch muscles Onset of Fatigue

70. Muscle Architecture Force production and velocity of shortening of the whole muscle depends on the architecture. It is important to remember that force is proportional to myofiber number, while velocity is proportional to myofiber length. Therefore, strap-like muscles provide the greatest velocity of shortening, while pennate muscles can generate more force.

71. Leverage  Because muscles operate across joints, the force applied to move an object depends on the leverage factor  LF = Leverage arm / Distance from joint  The farther away from the joint a muscle is inserted, the smaller the leverage factor and the easier it is to move an object (example: door hinge)  The closer a muscle is inserted to the joint, the larger the leverage factor (mechanical disadvantage), but the more maneuverable the object is

72. Preload, Afterload and the Latent Period (influence on twitch force) Preloaded with 10 kgAfterloaded with 10 kg 8 msec latent period 12 msec latent period Preloaded with 20 kg 8 msec latent period Afterloaded with 20 kg 20 msec latent period Action Potential Action Potential Action Potential Action Potential Muscle Twitch Muscle Twitch Muscle Twitch Muscle Twitch The latent period is prolonged in an after- loaded muscle because it takes time to stretch the series elastic component. The length of the latent period is dependent on load for afterloaded muscle, but independent of load for preloaded muscle. Increasing load decreases twitch shortening independent of effects on latent period. Extent of Shortening

73. Load-Velocity Relationship As load increases the velocity of shortening decreases.

74. Sample Question #3 A muscle which weighs 12 g and is 100 cm long is stimulated for a total of one hour at a frequency of 4/min. Upon each stimulation the muscle lifts 204 g and shortens 0.5 meters. What is the work and power output of that muscle?

75. Sample Question #3 A muscle which weighs 12 g and is 100 cm long is stimulated for a total of one hour at a frequency of 4/min. Upon each stimulation the muscle lifts 204 g and shortens 0.5 meters. What is the work and power output per hour of that muscle? Force produced per stimulation = 0.204 kg x 9.81 m/s 2 = 2.00124 N Work done during 1 contraction = 2 N x 0.5 m = 1.0 Joules Work done per hour = 1.0 J x 4/min x 60 min = 240 J Power output over 1 hour = 240 J / 3600 sec = 0.067 Watts Total work per gram of muscle = 240 J / 12 g = 20.0 J/g

76. Rate of Onset of Energy Pathways Aerobic Mechanisms Anaerobic Glycolysis Creatine Phosphate Percent Capacity of Energy Generating System Exercise Duration 10 sec. 30 sec.2 min.5 min. 100

77. Biochemical Profile Performance Profile Fiber Type Glycolytic Oxidative MHC-ATPase Fatigue Activity Profile Activity Twitch SpeedResistance Fast Twitch White V. High Low High Low Short term phasic IIB Fast Twitch Red Moderate V. High High High Sustained phasic IIA Slow Twitch Low Moderate Low V. High Sustained Tonic I Characteristics of Muscle Fiber Types The activity profile of the major muscle fiber types matches the biochemical and contractile profiles for these fiber types.

78. Anaerobic Threshold Oxygen Consumption (ml/kg/min) Exercise Work Load REST 30 45 60 100 20 40 60 80 Blood Lactate (mg/dL) Anaerobic Threshold UntrainedTrained

79. Oxygen Debt oxygen debt and oxygen repayment are equal Rate of Energy Expenditure Time (minutes) Oxygen Debt Oxygen Repayment Oxygen Consumption 028

80. Parameters of Endurance Training Time (months) Adaptive Ratio (Control/Trained) TCA Cycle Enzymes Oxidative Potential of Fast Fibers Capillary Density Slow twitch fiber diameter VO 2 Max 112246 Training De-training

81. Efficiency Calculations A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O 2. Baseline is 400 ml of O 2 /min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O 2 = 4.8 kcal 1 cal = 4.186 J

82. Efficiency Calculations A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O 2. Baseline is 400 ml of O 2 /min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O 2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal

83. Efficiency Calculations A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O 2. Baseline is 400 ml of O 2 /min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O 2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal Total E = 4 L x 4.8 kcal = 19.2 kcal Net E = (4 L – 0.4 L x 5 min) x 4.8 kcal = 9.6 kcal

84. Efficiency Calculations A 70-kg individual does 20 pullups, lifting his body weight 1 meter each time. In doing so, he consumes 4 liters of O 2. Baseline is 400 ml of O 2 /min. Total exercise time is 5 mins. What is his gross and net mechanical efficiency. 1 L O 2 = 4.8 kcal 1 cal = 4.186 J W = mgh = (70 x 9.8 x 1) x 20 reps = 13.7 kJ = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal = 13.7 kJ/4.186 kJ/kcal = 3.3 kcal Total E = 4 L x 4.8 kcal = 19.2 kcal Net E = (4 L – 0.4 L x 5 min) x 4.8 kcal = 9.6 kcal Gross Efficiency = W/E = 3.3 kcal/19.2 kcal = 17% Net Efficiency = 3.3/9.6 = 34%

85. Fiber Types

86. Smooth Muscle: Unitary  Present in GI tract, bladder, uterus, and ureter  Contracts in coordinated fashion b/c of gap jxns  Modulated by NT’s and hormones  Has pacemaker activity, slow waves

87. Smooth Muscle: Multiunit  Found in iris, ciliary muscels of lens, and the vas deferens  Cells don’t communicate w/ each other electrically  Densely innervated by autonomics

88. Excitation-Contraction in Smooth Muscle  1) Action potential opens Ca 2+ channels in sacrolemmal membrane  2) Rise in intracellular Ca 2+ concentration causes Ca 2+ bind to calmodulin - the Ca 2+ - Calmodulin complex binds to and activates myosin light chain kinase(MLCK)  3) Activated MLCK phosphorylates myosin, which can now form an break cross-bridges *amount of cross-bridges=tension=intracellular Ca 2+  4) Intracellular Ca 2+ decreases(b/c of SR’s Ca 2+ ATPase) and myosin is dephosphorylated by myosin light chain phosphatase(MLCP) Ratio of MLCK:MLCP is main determinant of tension in smooth muscle Ratio of MLCK:MLCP is main determinant of tension in smooth muscle

89. Practice Questions for Nerve/Muscle Physio Test 9/1/2004

90. Choose the correct sequence of events during excitation/contraction coupling: a) Action potential, calcium release, depolarization of the t-tubules, contraction, calcium re-uptake b) Action potential, depolarization of the t-tubules, calcium release, contraction, calcium re-uptake c) Action potential, depolarization of the t-tubules, calcium re-uptake, contraction, calcium release d) Action potential, calcium release, contraction, depolarization of the t-tubules, calcium re-uptake

91. Choose the correct sequence of events during excitation/contraction coupling: a) Action potential, calcium release, depolarization of the t-tubules, contraction, calcium re-uptake b) Action potential, depolarization of the t-tubules, calcium release, contraction, calcium re-uptake c) Action potential, depolarization of the t-tubules, calcium re-uptake, contraction, calcium release d) Action potential, calcium release, contraction, depolarization of the t-tubules, calcium re-uptake

92. At equilibrium the concentration of Na + is 5 mM inside the cell and 500 mM outside the cell. What is the Na + equilibrium potential for this cell? a) +90 mV b) -90 mV c) +120 mV d) -120 mV e) +60 mV

93. At equilibrium the concentration of Na + is 5 mM inside the cell and 500 mM outside the cell. What is the Na + equilibrium potential for this cell? a) +90 mV b) -90 mV c) +120 mV d) -120 mV e) +60 mV

94. According to the "size principle" which of the following statements would be true? a) large motor units are recruited first but generate less force b) large motor units are recruited first and generate more force c) small motor units are recruited first and generate more force d) small motor units are recruited first but generate less force e) motor unit size and force production are not related so none of the above are true.

95. According to the "size principle" which of the following statements would be true? a) large motor units are recruited first but generate less force b) large motor units are recruited first and generate more force c) small motor units are recruited first and generate more force d) small motor units are recruited first but generate less force e) motor unit size and force production are not related so none of the above are true.

96. According to the sliding filament theory, which of the following occurs during a muscle contraction: a) The thin filaments pull the H zone to the center of the sarcomere. b) The Z lines pull the thick filaments in the overlapping region. c) The area of overlap between the thick and thin filaments increases, however the actual lengths of the thick and the thin filaments remain unchanged. d) The width of both the I band and the A band decreases while the H zone increases.

97. According to the sliding filament theory, which of the following occurs during a muscle contraction: a) The thin filaments pull the H zone to the center of the sarcomere. b) The Z lines pull the thick filaments in the overlapping region. c) The area of overlap between the thick and thin filaments increases, however the actual lengths of the thick and the thin filaments remain unchanged. d) The width of both the I band and the A band decreases while the H zone increases.

98. Warming the blood supply to the hypothalamus causes a) shivering. b) increased pulmonary circulation. c) piloerection. d) increased cutaneous circulation. e) increased mesenteric circulation.

99. Warming the blood supply to the hypothalamus causes a) shivering. b) increased pulmonary circulation. c) piloerection. d) increased cutaneous circulation. e) increased mesenteric circulation.

100. Which of the following features are the same in the sympathetic and parasympathetic nervous system? a) Average length of preganglionic fibers. b) Average length of postganglionic fibers. c) Neurotransmitter in preganglionic fibers. d) Neurotransmitter in postganglionic fibers.

101. Which of the following features are the same in the sympathetic and parasympathetic nervous system? a) Average length of preganglionic fibers. b) Average length of postganglionic fibers. c) Neurotransmitter in preganglionic fibers. d) Neurotransmitter in postganglionic fibers.

102. a) 1.20 um b) 1.60 um c) 1.76 um d) 2.08 um e) Cannot be determined from above data. The following data are given for a skeletal muscle fiber: Length of thin filament: 0.8um Length of H-zone: 0.4um The muscle is stimulated under isotonic conditions and it shortens 20%. What is the approximate length of the sarcomere in the contracted muscle according to the sliding filament theory?

103. H-zone = 0.4 um Thin Filaments = 0.8 um

104. 0.8 + 0.8 + 0.4 = 2.0 um 2.0 x 80% = 1.6 um

105. a) 1.20 um b) 1.60 um c) 1.76 um d) 2.08 um e) Cannot be determined from above data. The following data are given for a skeletal muscle fiber: Length of thin filament: 0.8um Length of H-zone: 0.4um The muscle is stimulated under isotonic conditions and it shortens 20%. What is the approximate length of the sarcomere in the contracted muscle according to the sliding filament theory?

106. GOOD LUCK!!  http://www2.uic.edu/stud_orgs/prof/M1/courses/physiology/ http://www2.uic.edu/stud_orgs/prof/M1/courses/physiology/  jwalsh3@uic.edu jwalsh3@uic.edu  strent1@uic.edu strent1@uic.edu  dgolde1@uic.edu dgolde1@uic.edu  BIOCHEM REVIEW NEXT WEEK, SAME TIME, ROOM TBA… Obi Ekwenna and Jason Emer Obi Ekwenna and Jason Emer