SLwal7-B3 L32 The Action Potential in Muscle & Nerve PDF

32 The action potential in muscle & nerve ILOs By the end of this lecture, students will be able to 1. Relate movements of ions across the membrane to electric changes in response to a stimulus 2. Correlate the ion channels activity the phases of action potential 3. Discuss phase...

32 The action potential in muscle & nerve ILOs By the end of this lecture, students will be able to 1. Relate movements of ions across the membrane to electric changes in response to a stimulus 2. Correlate the ion channels activity the phases of action potential 3. Discuss phases of action potential in relevance to nerve-muscle excitability I- Action potential Action potential is a property of excitable cells (i.e., nerve, muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential. Action potentials have stereotypical size and shape, are propagating, and are all-or-none. Definitions a. Depolarization makes the membrane potential less negative (the cell interior becomes less negative). b. Hyperpolarization makes the membrane potential more negative (the cell interior becomes more negative). c. Inward current is the flow of positive charge into the cell. Inward current depolarizes the membrane potential. d. Outward current is the flow of positive charge out of the cell. Outward current hyperpolarizes the membrane potential. e. Threshold is the membrane potential at which the action potential is inevitable. At threshold potential, net inward current becomes larger than net outward current. The resulting depolarization becomes self-sustaining and gives rise to the upstroke of the action potential. If net inward current is less than net outward current, no action potential will occur (i.e., all-or- none response). II. Ionic basis of the nerve action potential (Figure 1) 1. Resting membrane potential is approximately −70 mV. Is the result of the high resting conductance to K+,which drives the membrane potential toward the K+ equilibrium potential. At rest, the Na+ channels are closed and Na+ conductance is low. 2. Depolarization of the action potential Inward current of Na+depolarizes the membrane potential to threshold. Page 1 of 5  Depolarization causes rapid opening of the activation gates of the Na + channels, and the Na+ conductance of the membrane promptly increases ( a positive feedback loop) (Figure 2a) The Na+ conductance becomes higher than the K+ conductance, and the membrane potential is driven toward the Na+ equilibrium potential of +65 mV, but does not quite reach primarily because the increase in Na+ conductance is short-lived. The Na+ channels rapidly enter a closed state called the inactivated state and remain in this state for a few milliseconds before returning to the resting state, when they again can be activated. In addition, the direction of the electrical gradient for Na+ is reversed during the overshoot because the membrane potential is reversed, and this limits Na+ influx. A third factor producing repolarization is the opening of voltage-gated K+ channels. Thus, the rapid depolarization during the upstroke is caused by an inward Na + current. The over shoot is the brief portion at the peak of the action potential when the membrane potential is positive. 3. Repolarization of the action potential Closure of the Na+ channels take place , and the Na+ conductance returns toward zero. K+channels open slowly and increases K+conductance to even higher levels than at rest. The combined effect of closing the Na+ channels and greater opening of the K+ channels makes the K+ conductance higher than the Na+ conductance, and the membrane potential is repolarized. Thus, repolarization is caused by an outward K+ current. 4. Undershoot (hyperpolarizing after potential) The K+ conductance remains higher than at rest for some time after closure of the Na+ channels. During this period, the membrane potential is driven very close to the K + equilibrium potential. The slow return of the K+ channels to the closed state explains the after- hyperpolarization, followed by a return to the resting membrane potential. Thus, voltage-gated K+ channels bring the action potential to an end and cause closure of their gates through a negative feedback process. (Figure 2b) Page 2 of 5 Figure 1; Nerve action potential and associated changes in Na + and K+ conductance. Figure 2; Feedback control in voltage-gated ion channels in the membrane. (a) Na+ channels exert positive feedback. (b) K+ channels exert negative feedback. Page 3 of 5 III. Refractory periods ( Excitability changes) 1. Absolute refractory period is the period during which another action potential cannot be elicited, no matter how large the stimulus. coincides with almost the entire duration of the action potential. (All depolarization and 1/3 to 2/3 of repolarization) Explanation: Recall that the inactivation gates of the Na+ channels are closed when the membrane potential is depolarized. They remain closed until repolarization occurs. No action potential can occur until the inactivation gates open. 2. Relative refractory period begins at the end of the absolute refractory period and continues until the membrane potential returns to the resting level. An action potential can be elicited during this period only if a larger than usual inward current is provided. Explanation: The K+conductance is highert han at rest, and the membrane potential is closer to the K+ equilibrium potential and, therefore, farther from threshold; more inward current is required to bring the membrane to threshold. IV. All-or-none” law It is possible to determine the minimal intensity of stimulating current (threshold intensity) that, acting for a given duration, will just produce an action potential. The threshold intensity varies with the duration; with weak stimuli it is long, and with strong stimuli it is short. The relation between the strength and the duration of a threshold stimulus is called the strength–duration curve. Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a pro- cess called adaptation. Once threshold intensity is reached, a full-fledged action potential is produced. Further increases in the intensity of a stimulus produce no increment or other change in the action potential as long as the other experimental conditions remain constant. The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude and form regardless of the strength of the stimulus if the stimulus is at or above threshold intensity. The action potential is therefore “all or none” in character and is said to obey the all-or-none law. V. Propagation of action potentials in nerve (Figure 3) Page 4 of 5  occurs by the spread of local currents to adjacent areas of membrane, which are then depolarized to threshold and generate action potentials. Figure 3; Unmyelinated axon showing spread of depolarization by local current flow. Box shows active zone where action potential had reversed the polarity. Conduction velocity is increased by: a. ↑fiber size. Increasing the diameter of a nerve fiber results in decreased internal resistance; thus, conduction velocity down the nerve is faster. b. Myelination. Myelin acts as an insulator around nerve axons and increases conduction velocity. Myelinated nerves exhibit saltatory conduction because action potentials can be generated only at the nodes of Ranvier, where there are gaps in the myelin sheath (Figure 4). Figure 4; Myelinated axon. Action potentials can occur at nodes of Ranvier. N.B. The action potential in skeletal muscle and the ionic fluxes that underlie them share distinct similarities to those in nerve, with quantitative differences in timing and magnitude. The resting membrane potential of skeletal muscle is about –90 mV. The action potential lasts 2 to 4 ms and is conducted along the muscle fiber at about 5 m/s. The absolute refractory period is 1 to 3 ms long, and the after-polarizations, with their related changes in threshold to electrical stimulation, are relatively prolonged. The distribution of ions across the muscle fiber membrane is similar to that across the nerve cell membrane. Page 5 of 5