1. Resting Membrane Potential
Esraa kiwan

3. Membrane Potential
Membrane potential: separation of opposite charges across the plasma membrane
difference in the relative number of cations (+ve) & anions (-ve) in the ICF & ECF
These separation produce energy differences between inside and outside which called potential
This energy is electrical energy and is measured by Millivolts

4. Membrane Potential
No membrane potential An equal number of (+ve) and (-ve) charges are on each side of the membrane
Membrane potential exist Unequal number of (+ve) and (-ve) charges are on each side of the membrane

5. Membrane Potential
Separated charges accumulated in a thin layer along the outer and inner surface of the plasma membrane

6. Membrane Potential
The magnitude of the potential depends on the degree of separation of the opposite charges
The greater the number of separated charges  the larger potential

7. Resting Membrane Potential
All plasma membrane of all living cells have resting membrane potential:
Varies in value according to the type of the cell:
Nerve cell  -70 mV
Skeletal and cardiac muscle  -80 to -90 mV
Smooth muscle  -60mV
The sign always represent the
polarity of the excess charge
on the inside of the membrane
Inside is more -ve than outside

8. Resting Membrane Potential
In the body, the electrical charges are carried by ions
The ions primarily responsible for the generation of resting membrane potential are:
Na +
K +
A - (-ve charged intracellular proteins)

10. Resting Membrane Potential
The electrical prosperities of the cell membrane are due to:
Unequal distribution of a key ions across the plasma membrane
Selective movement of these ions through plasma membrane

11. Resting membrane potential
Unequal distribution of a key ions between ICF and ECF are maintained by Na+ /K + pump:
Active transport mechanism
Pumps 3Na+ outside, 2K+ inside
Maintains high [K+] inside the cell, high [Na+] outside
Unequal transport generates a membrane potential
Outside becoming more +ve than inside (more +ve are transported out than in)

12. Resting membrane potential
80% of resting membrane potential is caused by the passive diffusion of K + and Na + down concentration gradient
Na + & K + concentration gradient maintained by Na + /K + pump
K + permeability
about X than
for Na +
K + ions influence
the resting membrane
potential than Na +
Na + / K + pump responsible of 20% of resting membrane potential through maintaing concentration gradient for Na +, K +

13. Resting Membrane Potential
Electrochemical gradient for Na+, K+ in resting state:
Concentration gradient:
Na +  inside
K +  outside
Electrical gradient ( toward the negative charge)
K +  inside

14. Resting Membrane Potential
K + equilibrium potential (EK+ ):

15. Resting Membrane Potential
Na + equilibrium potential (ENa+ ):

16. Resting Membrane Potential
Effect of both K + and Na + on resting membrane potential:
Na + equilibrium potential (ENa+)= +60 mV
K + equilibrium potential (EK+ )= -90 mV
K + exerts the dominant effect on the resting membrane potential, because the membrane is more permeable to K +  resting membrane potential is much closer to EK+ than to ENa+ which is -70mV

17. Changes in Resting Membrane Potential
Excitable cell (Nerve & muscle) able to undergo transient, repaid changes in their resting membrane potential
These changes serve as electrical signal:
Nerve cell: use electrical signal to receive, process, initiate, and transmit messages
Muscle: these electrical signals initiate contraction

18. Changes in Resting Membrane Potential
Polarization: separation of opposite charge i.e. resting state (-ve inside compared with outside)
Depolarization: decrease the negativity of the membrane ( moving toward 0 mV)
Repolarization: the membrane returns to resting potential
Hyperpolarization: the membrane become more negative than at rest (increase negativity)

19. Changes in Resting Membrane Potential
Changes in ions movement a cross the membrane (changes in membrane permeability):
If net inward of +ve increases compared to the resting state, the membrane become depolarize (decrease -ve inside)
If net outward of +ve increases compared to the resting state, the membrane become hyperpolarized (increase -ve inside)

20. Changes in resting membrane potential
Changes in membrane potential could be:
Graded potential
Action potential

21. Action Potential Brief, repaid, large changes in membrane potential
During action potential the potential actually reverses the inside of the cell become more +ve than outside

22. Action Potential Stages of action potential
Triggering event causes the membrane
to depolarize from resting potential
(-70 mV)
Depolarization proceeds slowly at first,
until it reaches a critical level,
(threshold potential) (-50 _ -55 mV)
At threshold potential, an explosive
depolarization takes place:
Upward deflection to +30mV
Reversal of polarity( the inside of the cell becomes more +ve than outside)
Then, the membrane repolarizes, dropping back to resting potential

23. Action Potential
Action Potential is caused by marked changes in membrane permeability of ions:
At rest, membrane permeability to K + is much higher than it for Na +
So, K + makes the greatest contribution to the resting membrane potential.
This will completely change during action potential, due to activation of Voltage-Gated Na + & K + Channels

24. Action Potential Voltage Gated Channels
The channels that their state (opening or closure) depends on the voltage changes of the membrane
At resting potential, all the Voltage-Gated Channels are closed

25. Action potential
 When a membrane starts to depolarize toward threshold, some of the voltage-gated Na+ channels will open
Then, Na+ will move down its electrochemical gradient into the cell
This influx of Na+ will
depolarize the membrane
more, & so more channels
will open… & so on

26. Action potential
At threshold, there is an explosive increase in permeability of Na+ (≈600 times more permeable to Na+ than to K+)
The membrane potential will become closer to ENa+= +60 mV
The potential will be (+30 mV)
Before reaching the Peak-Potential, Na+ channels will be inactivated, so no more Na+ leak to the inside

28. Action potential
Simultaneous with inactivation of Na+ channels, the voltage-gated K+ channels starts to slowly open, with maximum opening occurring at the peak of action potential
These channels will greatly increase the K+ permeability (≈300 times more than Na+)
This will lead to marked efflux of K+ out of the cell, down its concentration gradient
This will rapidly restore the negative resting potential

29. Action potential
Rising phase: from threshold to (+30 mV) is caused by Na+ influx
Falling phase: from (+30 mV) to resting potential is caused by K+ efflux
Ions distribution is restored by the action of Na+-K+ pump

32. Action potential Action Potential is an all-or-none response
If the membrane is not depolarized to its threshold level, no action potential is produced
If the stimulus strength is increased more than what is needed to produce action potential there will be no change in magnitude of action potential (produce same action potential)
Strong stimulus produces more action potential frequancy (increase in #), and cause more cells to reach their threshold

33. Action potential
Propagation of action potential throughout nerve fiber
Once action potential is generated in any part of neuron, it will propagated all the way through the axon to reach axon terminal
Action potential spreads throughout
the membrane in undecresing fashion
(non-decremental)

34. Neuron

35. Action potential
Propagation of action potential throughout nerve fiber
Contiguous conduction in unmyelinated fibers:
Action potential at one point will excited the adjacent point by increasing the permeability of adjacent point to Na+ causing generation of Action Potential

36. Action potential
Propagation of action potential throughout nerve fiber
Saltatory conduction in myelinated fibers

37. Refractory Period
A period during which a new action potential cannot be initiated by normal events in a region that has just undergone an action potential
Two phases:
Absolute Phase: a second action potential can’t be produced, no matter how strong is the stimulus. The membrane completely unresponsive to second stimulus at all
Relative Phase: during which the second action potential can be produced only by an exceptionally strong triggering

38. Prosperities of Action Potential
Is an “all or none” event (either pass threshold or dosen’t)
Is propagated down the axon in nondecremental fashion
Has a fixed amplitude ( action potential do NOT change in Height)
Has a refractory period (in which stimulation will not produce an action potential)

39. Graded Potential
Is a local change in the membrane potential that occurs in varying grades (changes may be 10 or 20 mV)
The magnitude vary with the strength of the stimulus, the stronger the triggering event  the larger the graded potential
The magnitude of the graded potential continues to decrease the farther it moves away from the initial active area. (Decremental)
Graded potential do not have a refractory period

40. A neuron may terminate at:
A muscle
A gland
Another neuron

41. Synaptic Transmission
A synapse is the junction between two neurons
It involves the junction between an axon terminal of one neuron (presynaptic neuron), & the dendrites or the cell body of a second neuron (postsynaptic neuron)

42. Synaptic Transmission
The action potential (the electrical signal) crosses the synapse by chemical means to induce electrical changes in other neuron
The chemicals released from one neuron to induce electrical changes in next neuron are neurotransmitters
Acetylcholine
Norepinephrine
Histamine
Glycine
Gamma-aminobutyric acid (GABA)
Synapses operate in one direction only

44. Synaptic Transmission
Events taking place in a synapse:
Propagation of an action potential to the axon terminal of a presynaptic neuron
The arriving action potential produces an influx of calcium ions through voltage-dependent calcium ion channels. ([Ca+2] in ECF is much higher than that inside the synaptic knob)
Ca+2 induces the release by exocytosis of neurotransmitters from synaptic vesicles into the synaptic cleft
After diffusing across the cleft, the neurotransmitter binds with its receptor sites on the subsynaptic membrane
This binding triggers the opening of specific ion channels in the subsynaptic membrane. This alters the permeability of the postsynaptic neuron (Chemical messenger-gated channels)

46. Synaptic Transmission
The changes in postsynaptic neuron by neurotransmitter could be
excitatory or inhibitory

47. Types of synapses Excitatory synapse:
the response to the receptor-neurotransmitter combination is an opening of Na+ & K + channels within the subsynaptic membrane.
Na+ moves into the postsynaptic neuron & K + out of it, but to a less extent
The result is a net movement of positive ions into the cell  Small depolarization in the postsynaptic neuron
Activation of one excitatory synapse can rarely depolarize the postsynaptic membrane sufficiently to bring it to threshold, but it brings it closer to threshold
This postsynaptic potential change is called: Excitatory PostSynaptic Potential (EPSP)

48. Types of synapses Inhibitory synapse:
The response to the receptor-neurotransmitter combination is an opening of K+ & Cl - channels within the subsynaptic membrane
The resulting ion movements bring about a small hyperpolarization of the postsynaptic neuron (greater internal negativity)
This moves the membrane potential away from threshold
This small hyperpolarization of the postsynaptic cell is called: Inhibitory PostSynaptic Potential (IPSP)

49. Synaptic Transmission
The time needed for action potential to cause the release of the neurotransmitter into synaptic cleft and produce its effect on postsynaptic neuron is called synaptic delay, its about msec

50. Synaptic Transmission
Fate of neurotransmitter that released from presynaptic membrane:
Uptake of the neurotransmitter into the cytoplasm of the presynaptic membrane (reused again)
Enzymatic deactivation: inactivation of neurotransmitter by certain enzyme

51. Synaptic Transmission
Grand PostSynaptic Potential (GPSP): summation of all potentials ( both EPSP + IPSP) that occur at the same time
The postsynaptic neuron can be brought to threshold by:
Temporal summation: is the summing of several EPSPs occurring very close together in time because of successive firing of a single presynaptic neuron
Spatial summation: is the summation of EPSPs originating simultaneously from several different presynaptic inputs (from different points in space)
If an excitatory & an inhibitory input are simultaneously activated, the concurrent EPSP & IPSP more or less cancel each other out.

53. Neuromuscular Junction

54. Neuromuscular Junction

55. Neuromuscular Junction

56. Neuromuscular Junction
Factors affect transmission of impulse from nerve fiber to muscle fiber at neuromuscular junction:
Botulinum toxin: blocks the release of Ach from nerve terminal. Inability of nerve impulses to pass to muscle cause muscle paralysis
Venom of black widow spiders: explosive release of Ach at neuromuscular junction causing persistent contraction of muscle
Organophosphates: inhibit AchE leading to continuous muscle contraction (leading to death because of respiratory failure)
Curare: binds with Ach receptors on the motor end plate, so the released Ach cant bind its receptors leading to paralysis
Mysthenia gravis: decrease in Ach receptors so less activation to muscle leading to weakness

58. Muscle 3 Types of Muscles
1. Smooth – involuntary, unstriated (not banded)
- controlled by autonomic system
2. Cardiac – involuntary, striated
3. Skeletal – voluntary, striated

59. Structure of Skeletal Muscle

60. Structure of Skeletal Muscle
A band: consists of thick filaments along with the portions of the thin filaments that overlap on both ends of the thick filaments
I band: consists of the remaining portion of the thin filaments that
do not project into the A band
H zone: The lighter area within the middle of the A band where the thin filaments do not reach

61. Structure of Skeletal Muscle
Z line: Visiblel line in the middle of each I band, flattened disc-like cytoskeletal protein that connects the thin filaments
Sarcomere: The area between two Z lines (functional unit of skeletal muscle)
M line: extends vertically down the middle of the A band within the center of the H zone

62. Structure of Skeletal Muscle
Thick filaments
Myosin forms the thick filaments
A myosin molecule is a protein consisting of two identical subunits
The protein’s tail ends are intertwined around each other, with the two globular heads projecting out at one end
These heads form the cross bridges between the
thick and thin filaments
Each cross bridge has two important sites
important to the contractile process: an actin
binding site and a myosin ATPase site

63. Structure of Skeletal Muscle
Thin filaments

64. Structure of Skeletal Muscle
Thin filaments
Composed of 3 proteins: actin, tropomyosin, and troponin
Actin :
the primary structural proteins of the thin filament (It forms the backbone of the thin filament)
Actin spherical in shape.; joined into two strands and twisted together
Each actin molecule has a special binding site for attachment with a myosin cross bridge

65. Structure of Skeletal Muscle
Thin filaments
Tropomyosin:
Threadlike proteins that lie end to end alongside the groove of the actin spiral
Tropomyosin covers the actin sites that bind with the cross bridges thus blocking the interaction that leads to muscle contraction
Tropomyosin is stabilized in this blocking position by troponin molecules, which fasten down the ends of each tropomyosin molecule
Troponin:
protein complex consisting of 3 units:
Troponin T: that binds to tropomyosin
Troponin I: that binds to actin inhibitin the interaction between Actin & myosin
Troponin C: that can bind with Ca2+ (When Ca2+ binds to troponin, the shape of this protein is changed in such a way that tropomyosin is allowed to slide away from its blocking position)

66. Structure of Skeletal Muscle
Contractile proteins:
Actin and Myosin
Binding of actin and myosin molecules at the cross bridges results in energy-consuming contraction of the muscle fiber
Regulatory proteins:
Tropomyosin and Troponin
Covering the binding sites for cross-bridge interaction between actin and myosin (preventing contraction)
Exposing the binding sites for cross-bridge interaction between actin and myosin (permitting contraction)

67. Skeletal Muscle Contraction
Sliding filament mechanism:
Contraction is accomplished by the thin filaments sliding closer together between the thick filament

68. Skeletal Muscle Contraction
Sliding filament mechanism:

69. Skeletal Muscle Contraction
Cross bridge activity:

70. Skeletal Muscle Contraction

71. Skeletal Muscle Contraction