PHYSIOLOGY OF NERVE AND MUSCLE CELLS lecture 3

PHYSIOLOGY OF NERVE AND MUSCLE CELLS :
O B J E C T I V E S :
AT THE END OF THE LECTURE YOU SHOULD BE ABLE TO
•Recognize the nerve cell response to excitation.
•Understand the way that nerve impulse is normally transmitted.
•Identify the electrical and chemical changes (ionic channels) that underlie the action potential.
Action potential
The action potential is a phenomenon of excitable cells, such as nerve and muscle, and consists of a rapid depolarization (upstroke) followed by repolarization of the membrane potential. Action potentials are the basic mechanism for transmission of information in the nervous system and in all types of muscle.
NERVE ACTION POTENTIAL:
•AP begins with a sudden change from the normal negative to a positive RMP and then back to the negative potential.
•AP moves along the nerve fiber with transfer of positive charges to the interior of the fiber at its onset and return of positive charges to the exterior at its end,
•Until it comes to the fiber s end, conducting a nerve signal.
NERVE ACTION POTENTIAL:
Depolarization is the process of making the membrane potential less negative, the usual resting membrane potential of excitable cells is oriented with the cell interior negative. Depolarization makes the interior of the cell less negative, or it may even cause the cell interior to become positive.
Hyperpolarization is the process of making the membrane potential more negative. As with depolarization.
NERVE ACTION POTENTIAL:
Inward current is the flow of positive charge into the cell. Thus, inward currents depolarize the membrane potential. An example of an inward current is the flow of Na+ into the cell during the upstroke of the action potential.
Outward current is the flow of positive charge out of the cell. Outward currents hyperpolarize the membrane potential. An example of an outward current is the flow of K+ out of the cell during the repolarization phase of the action potential.
•Threshold potential is the membrane potential at which occurrence of the action potential is inevitable. Because the threshold potential is less negative than the resting membrane potential, an inward current is required to depolarize the membrane potential to threshold. At threshold potential, net inward current (e.g., inward Na+ current) becomes larger than net outward current (e.g., outward K+ current), and the resulting depolarization becomes self-sustaining, giving rise to the upstroke of the action potential. If net inward current is less than net outward current, the membrane will not be depolarized to threshold, and no action potential will occur (see all-or-none response).
•Overshoot is that portion of the action potential where the membrane potential is positive (cell interior positive).
•Undershoot, or hyperpolarizing afterpotential, is that portion of the action potential, following repolarization, where the membrane potential is actually more negative than it is at rest.
•Refractory period is a period during which another normal action potential cannot be elicited in an excitable cell. Refractory periods can be absolute or relative.
IONIC BASIS OF THE ACTION POTENTIAL
•The action potential is a fast depolarization (the upstroke), followed by repolarization back to the resting membrane potential , which occur in the following steps:
•Resting membrane potential. At rest, the membrane potential is approximately -70 mV (cell interior negative). The K+ conductance or permeability is high and K+ channels are almost fully open, allowing K+ ions to diffuse out of the cell down the existing concentration gradient. This diffusion creates a K+ diffusion potential, which drives the membrane potential toward the K+ equilibrium potential. At rest, the Na+ conductance is low, and, thus, the resting membrane potential is far from the Na+ equilibrium potential.
•Upstroke of the action potential. An inward current, usually the result of current spread from action potentials at neighboring sites, causes depolarization of the nerve cell membrane to threshold, which occurs at approximately -60 mV. This initial depolarization causes rapid opening of the activation gates of the Na+ channel, and the Na+ conductance promptly increases and becomes even higher than the K+ conductance The increase in Na+ conductance results in an inward Na+ current; the membrane potential is further depolarized toward, but does not quite reach, the Na+ equilibrium potential of +65 mV..
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•Repolarization of the action potential. The upstroke is terminated, and the membrane potential repolarizes to the resting level as a result of two events. First, the inactivation gates on the Na+ channels respond to depolarization by closing, but their response is slower than the opening of the activation gates. Thus, after a delay, the inactivation gates close the Na+ channels, terminating the upstroke. Second, depolarization opens K+ channels and increases K+ conductance to a value even higher than occurs at rest. The combined effect of closing of the Na+ channels and greater opening of the K+ channels makes the K+ conductance much higher than the Na+ conductance. Thus, an outward K+ current results, and the membrane is repolarized.
•Hyperpolarizing after potential (undershoot). For a brief period following repolarization, the K+ conductance is higher than at rest, and the membrane potential is driven even closer to the K+ equilibrium potential (hyperpolarizing afterpotential). Eventually, the K+ conductance returns to the resting level, and the membrane potential depolarizes slightly, back to the resting membrane potential. The membrane is now ready, if stimulated, to generate another action potential.

CHARACTERISTICS OF ACTION POTENTIALS
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•Stereotypical size and shape. Each normal action potential for a given cell type looks identical, depolarizes to the same potential, and repolarizes back to the same resting potential.
•Propagation. An action potential at one site causes depolarization at adjacent sites, bringing those adjacent sites to threshold. Propagation of action potentials from one site to the next is nondecremental.
•All-or-none response. An action potential either occurs or does not occur. If an excitable cell is depolarized to threshold in a normal manner, then the occurrence of an action potential is inevitable. On the other hand, if the membrane is not depolarized to threshold, no action potential can occur. Indeed, if the stimulus is applied during the refractory period, then either no action potential occurs, or the action potential will occur but not have the stereotypical size and shape.
•The required actor in causing depolarization and repolarization of the nerve membrane during AP is the voltage-gated Na+ channel.
•A voltage-gated K+ channel also plays an important role in increasing the rapidity of repolarization of the membrane.
Voltage-Gated Sodium and Potassium Channels:
•When depolarization, the membrane potential becomes less negative,
•A sudden conformational change in the activation gate of the Na+ channel, flipping it all the way to the open position “activated state”.
•Na+ pour inward through the channel, increasing the Na+ permeability of the membrane as much as 500 – 5000 folds (Na+ influx).
•Same voltage that opens the activation gate also closes the inactivation gate, however, a few 10,000ths of a second later.
Voltage-Gated Sodium and Potassium Channels:
•Na+ ions no longer can pour to the inside of the membrane “inactivated state” .
•At this point, the membrane potential begins to recover back toward the resting membrane state, “repolarization process”.
• The inactivation gate will not reopen until the membrane potential returns to or near the original RMP.
•Therefore, it is usually not possible for the Na+ channels to open again without first repolarizing the nerve fiber.
Voltage-Gated Sodium and Potassium Channels:
•During the resting state, the gate of K+ channel is closed and K+ are prevented from passing to the exterior.
•Depolarization causes a conformational opening of the gate; yet slowly, allowing increased K+ diffusion outward (K+ efflux).
•Because of the slight delay, they open just at the time of the Na+ channels inactivation.
•At the end of AP, the return of the membrane potential to the negative state causes the K+ channels to close back to their original status.
•Thus, the decrease in Na+ entry to the cell and the simultaneous increase in K+ exit from the cell combine to speed the repolarization process.
Voltage-Gated Sodium and Potassium Channels:
Electrogenesis of the Action Potential
•The nerve cell membrane is polarized at rest, with positive charges lined up along the outside of the membrane and negative charges along the inside. During the action potential, this polarity is abolished and for a brief period is actually reversed, Positive charges from the membrane ahead of and behind the action potential flow into the area of negativity represented by the action potential ("current sink"). By drawing off positive charges, this flow decreases the polarity of the membrane ahead of the action potential. Such electrotonic depolarization initiates a local response, and when the firing level is reached, a propagated response occurs that in turn electrotonically depolarizes the membrane in front of it