Action Potential PDF

Week 2: Action Potential Refractory periods During the refractory periods, excitable cells are incapable of producing normal action potentials (see Fig. 1.13). The refractory period includes an absolute refractory period and a relative refractory period. Absolute refractory period The absolute ref...

Week 2: Action Potential Refractory periods During the refractory periods, excitable cells are incapable of producing normal action potentials (see Fig. 1.13). The refractory period includes an absolute refractory period and a relative refractory period. Absolute refractory period The absolute refractory period overlaps with almost the entire duration of the action potential. During this period, no matter how great the stimulus, another action potential cannot be elicited. The basis for the absolute refractory period is closure of the inactivation gates of the Na⁺ channel in response to depolarization. These inactivation gates are in the closed position until the cell is repolarized back to the resting membrane potential, and the Na⁺ channels have recovered to the “closed, but available” state (see Fig. 1.14). Relative refractory period The relative refractory period begins at the end of the absolute refractory period and overlaps primarily with the period of the hyperpolarizing afterpotential. During this period, an action potential can be elicited, but only if a greater than usual depolarizing (inward) current is applied. The basis for the relative refractory period is the higher K⁺ conductance than is present at rest. Because the membrane potential is closer to the K⁺ equilibrium potential, more inward current is needed to bring the membrane to threshold for the next action potential to be initiated. Accommodation When a nerve or muscle cell is depolarized slowly or is held at a depolarized level, the usual threshold potential may pass without an action potential having been fired. This process, called accommodation, occurs because depolarization closes inactivation gates on the Na⁺ channels. If depolarization occurs slowly enough, the Na⁺ channels close and remain closed. The upstroke of the action potential cannot occur because there are insufficient available Na⁺ channels to carry inward current. An example of accommodation is seen in persons who have an elevated serum K⁺ concentration, or hyperkalemia. At rest, nerve and muscle cell membranes are very permeable to K⁺; an increase in extracellular K⁺ concentration causes depolarization of the resting membrane (as dictated by the Nernst equation). This depolarization brings the cell membrane closer to threshold and would seem to make it more likely to fire an action potential. However, the cell is actually less likely to fire an action potential because this sustained depolarization closes the inactivation gates on the Na⁺ channels (Box 1.3). Propagation of action potentials Propagation of action potentials down a nerve or muscle fiber occurs by the spread of local currents from active regions to adjacent inactive regions. Figure 1.15 shows a nerve cell body with its dendritic tree and an axon. At rest, the entire nerve axon is at the resting membrane potential, with the cell interior negative. Action potentials are initiated in the initial segment of the axon nearest the nerve cell body. They propagate down the axon by the spread of local currents, as illustrated in the figure. Week 2: Action Potential Image 1.15 Spread of depolarization down a nerve fiber by local currents. A, The initial segment of the axon has fired an action potential, and the potential difference across the cell membrane has reversed to become inside positive. The adjacent area is inactive and remains at the resting membrane potential, inside negative. B, At the active site, positive charges inside the nerve flow to the adjacent inactive area. C, Local current flow causes the adjacent area to be depolarized to threshold and to fire action potentials; the original active region has repolarized back to the resting membrane potential In Figure 1.15 A, the initial segment of the nerve axon is depolarized to threshold and fires an action potential (the active region). As the result of an inward Na⁺ current, at the peak of the action potential, the polarity of the membrane potential is reversed and the cell interior becomes positive. The adjacent region of the axon remains inactive, with its cell interior negative. Figure 1.15 B illustrates the spread of local current from the depolarized active region to the adjacent inactive region. At the active site, positive charges inside the cell flow toward negative charges at the adjacent inactive site. This current flow causes the adjacent region to depolarize to threshold. In Figure 1.15 C, the adjacent region of the nerve axon, having been depolarized to threshold, now fires an action potential. The polarity of its membrane potential is reversed, and the cell interior becomes positive. At this time, the original active region has been repolarized back to the resting membrane potential and restored to its inside-negative polarity. The process continues, transmitting the action potential sequentially down the axon. Conduction velocity The speed at which action potentials are conducted along a nerve or muscle fiber is the conduction velocity. This property is of great physiologic importance because it determines the speed at which information can be transmitted in the nervous system. To understand conduction velocity in excitable Week 2: Action Potential tissues, two major concepts must be explained: the time constant and the length constant. These concepts, called cable properties, explain how nerves and muscles act as cables to conduct electrical activity. The time constant (τ) is the amount of time it takes following the injection of current for the potential to change to 63% of its final value. In other words, the time constant indicates how quickly a cell membrane depolarizes in response to an inward current or how quickly it hyperpolarizes in response to an outward current. Thus: τ = Rₘ Cₘ τ = Time constant Rₘ = Membrane resistance Cₘ = Membrane capacitance Two factors affect the time constant. The first factor is membrane resistance (Rₘ). When Rₘ is high, current does not readily flow across the cell membrane, which makes it difficult to change the membrane potential, thus increasing the time constant. The second factor, membrane capacitance (Cₘ), is the ability of the cell membrane to store charge. When Cₘ is high, the time constant is increased because injected current first must discharge the membrane capacitor before it can depolarize the membrane. Thus the time constant is greatest (i.e., takes longest) when Rₘ and Cₘ are high. The length constant (λ) is the distance from the site of current injection where the potential has fallen by 63% of its original value. The length constant indicates how far a depolarizing current will spread along a nerve. In other words, the longer the length constant, the farther the current spreads down the nerve fiber. Thus λ ∝ √(Rₘ / Rᵢ) Where: λ = Length constant Rₘ = Membrane resistance Rᵢ = Internal resistance Again, Rₘ represents membrane resistance. Internal resistance, Rᵢ, is inversely related to the ease of current flow in the cytoplasm of the nerve fiber. Therefore the length constant will be greatest (i.e., current will travel the farthest) when the diameter of the nerve is large, when membrane resistance is high, and when internal resistance is low. In other words, current flows along the path of least resistance. Changes in conduction velocity There are two mechanisms that increase conduction velocity along a nerve: increasing the size of the nerve fiber and myelinating the nerve fiber. These mechanisms can best be understood in terms of the cable properties of time constant and length constant. Week 2: Action Potential ♦ Increasing nerve diameter. Increasing the size of a nerve fiber increases conduction velocity, a relationship that can be explained as follows: Internal resistance, Rᵢ, is inversely proportional to the cross-sectional area (A = πr²). Therefore the larger the fiber, the lower the internal resistance. The length constant is inversely proportional to the square root of Rᵢ (refer to the equation for length constant). Thus the length constant (λ) will be large when internal resistance (Rᵢ) is small (i.e., fiber size is large). The largest nerves have the longest length constants, and current spreads farthest from the active region to propagate action potentials. Increasing nerve fiber size is certainly an important mechanism for increasing conduction velocity in the nervous system, but anatomic constraints limit how large nerves can become. Therefore a second mechanism, myelination, is invoked to increase conduction velocity. ♦ Myelination. Myelin is a lipid insulator of nerve axons that increases membrane resistance and decreases membrane capacitance. The increased membrane resistance forces current to flow along the path of least resistance of the axon interior rather than across the high resistance path of the axonal membrane. The decreased membrane capacitance produces a decrease in time constant; thus at breaks in the myelin sheath (see following), the axonal membrane depolarizes faster in response to inward current. Together, the effects of increased membrane resistance and decreased membrane capacitance result in increased conduction velocity (Box 1.4). If the entire nerve were coated with the lipid myelin sheath, however, no action potentials could occur because there would be no low resistance breaks in the membrane across which depolarizing current could flow. Therefore it is important to note that at intervals of 1 to 2 mm, there are breaks in the myelin sheath, at the nodes of Ranvier. At the nodes, membrane resistance is low, current can flow across the membrane, and action potentials can occur. Thus conduction of action potentials is faster in myelinated nerves than in unmyelinated nerves because action potentials “jump” long distances from one node to the next, a process called saltatory conduction.