In response to a depolarizing stimulus, some of the voltage-gated Na+ channels become active, and when the threshold potential is reached, the voltage-gated Na+ channels overwhelm the K+ and other channels and an action potential results (a positive feedb Renaissance History ack loop). The membrane potential moves toward the equilibrium potential for Na+ (+60 mV) but does not reach it during the action potential, primarily because the increase in Na+ conductance is short-lived. The sodium ion channels rapidly get closed called the inactivated state .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. This opening is slower and more prolonged than the opening of the Na+ channels, and consequently, much of the increase in K+ conductance comes after the increase in Na+ conductance. The net movement of positive charge out of the cell due to K+ efflux at this time helps complete the process of repolarization. The slow return of the K+ channels to the closed state also 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. Distribution of Ion Channels in Myelinated Neurons The spatial distribution of ion channels along the axon plays a key role in the initiation and regulation of the action potential. Voltage-gated Na+ channels are highly concentrated in the nodes of Ranvier and the initial segment in myelinated neurons. The initial segment and, in sensory neurons, the first node of Ranvier are the sites where im Renaissance History pulses are normally generated, and the other nodes of Ranvier are the sites to which the impulses jump during saltatory conduction which is responsible for faster impulse conduction in myelinated neurons. The number of Na+ channels per square micrometer of membrane in myelinated mammalian neurons has been estimated to be 50–75 in the cell body, 350–500 in the initial segment, less than 25 on the surface of the myelin, 2000–12,000 at the nodes of Ranvier, and 20–75 at the axon terminals. Along the axons of unmyelinated neurons, the number is about 110. 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 w>