Conduction of the action potential

A typical neuron consists of four functional regions  

Without ion flux, action potentials cannot be generated in the regions covered with myelin. Instead, they occur only at breaks in the myelin sheath 

Saltatory conduction results in a significant increase in the velocity of conduction of the nerve impulse down the axon compared to that of local current flow in an unmyelinated axon (see Table 4.2). The speed of conduction is 

The functional significance of myelin is revealed by the neurological deficits observed in patients with multiple sclerosis. This disorder is caused by the demyelination of neurons in the brain, spinal cord, and optic nerve. The loss of myelin disrupts the normal conduction of impulses along the axons of these neurons and results in weakness, numbness, loss of bladder control, and visual disturbances. 

A second factor that influences the velocity of action potential conduction is the diameter of the axon. The greater the diameter is then, the lower the resistance to current flow along the axon. Therefore, the impulse is 

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Conduction of the action potential in myelinated axons is called saltatory conduction. Because ion flux only occurs at the nodes of Ranvier, the action potential jumps, in effect, from node to node. This provides two advantages, speeding the rate of conduction and reducing the metabolic cost of an action potential, because energy-dependent ion transporters are not needed along myelinated segments. 

Generally, it is always only a very small part of the membrane that is depolarized during an action potential. The process can therefore be repeated again after a short refractory period, when the nerve cell is stimulated again. Conduction of the action potential on the surface of the nerve cell is based on the fact that the local increase in the membrane potential causes neighboring voltage-gated ion channels to open, so that the membrane stimulation spreads over the whole cell in the form of a depolarization wave. 

Conduction velocity of an action potential can be increased dramatically by the presence of myelin, a fatty sheath that surrounds the axon and that is interrupted into gaps every millimeter or so at the nodes of Ranvier. Myelin is elaborated by Schwann cells in the peripheral nervous system and by oligodendrocytes in the central nervous system (the biochemistry of myelin will be discussed later in the article). The presence of myelin will dramatically alter the mode and velocity of conduction of the action potential in the axon. As in unmyelinated nerves, the action potential is still transmitted from one section of the axon to another by the presence of local circuit currents. However, the fatty sheath of myelin has poor conduction properties and therefore acts as an insulator. Hence, the local circuit currents jump from one gap to another at the nodes of Ranvier and the rate of conduction is enhanced as local circuit currents travel faster than the action potential itself This process of discontinuous conduction is known as saltatory conduction. Numerous diseases involving myelin deficiency have been described clinically. As one might predict, demyelinating diseases have profound effects on neuronal conduction and on the well-being of the patient. A few of these conditions will be described briefly in the upcoming section on myelin biochemistry. 

Conductivity. Conductivity is an electrical property of excitable tissue which ensures that if one area of a membrane is excited to full activity, that area excites adjacent areas. Conduction of an impulse varies direcdy with the rate of development of phase 0 and the ampHtude of the action potential. Phase 0 is faster, and ampHtude of the action potential is greater, the more negative the transmembrane potential at the time of initiation of the impulse. Conduction velocity is faster when phase 0 is fast. 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

Cardiac IKi is the major K+ current responsible for stabilizing the resting membranepotential and shaping the late phase of repolarization of the action potential in cardiac myocytes. The name should not be confused with that of an Intermediate conductance calcium-activated K+ channel, which sometimes is also called IK1. 

Action potentials, self-propagating. Action potentials of smooth muscle differ from the typical nerve action potential in at least three ways. First, the depolarization phases of nearly all smooth muscle action potentials are due to an increase in calcium rather than sodium conductance. Consequently, the rates of rise of smooth action potentials are slow, and the durations are long relative to most neural action potentials. Second, smooth muscle action potentials arise from membrane that is autonomously active and tonically modulated by autonomic neurotransmitters. Therefore, conduction velocities and action potential shapes are labile. Finally, smooth muscle action potentials spread along bundles of myocytes which are interconnected in three dimensions. Therefore the actual spatial patterns of spreading of the action potential vary. 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

Young. I think gap junctions are very important in the initiation of labour. It has been shown that they increase the conduction rate of the action potential prior to the onset of labour. They seem to be induced prior to the initiating event in labour. You can have the gap junctions and the rapid action potential propagation, yet no spontaneous labour. Therefore they are necessary, but not sufficient. If I look at intercellular waves, as I flow the solution across, there is about a five cell communication that goes against the flow. In other words it has an intracellular mechanism, and it seems to be about four or five cells that go against the flow and the rest go with the flow. 

Sanders Is the shortening of the plateau of the action potential due to activation of the long conductance Ca2+-activated K+ (BK) channels ... 

Cardiac APD is controlled by a fine balance between inward and outward currents in the repolarization phase. Since outward K+ currents, especially the delayed rectifier repolarizing current, IK (which is the sum of two kinetically and pharmacologically distinct types of K+ currents a rapid, 1k and a slow, IKs, component), play an important role during repolarization and in determining the configuration of the action potential, small changes in conductance can significantly alter the effective refractory period, hence the action potential duration. 

Conduction of an action potential through the terminal branches of an axon causes depolarization of the varicosity membrane, resulting in the release of transmitter molecules via exocytosis. Once in the junctional extracellular space (biophase), acetylcholine interacts with cholinoreceptors. 

Disopyramide reduces membrane responsiveness in atrial muscle and the amplitude of the action potential. Excitability of atrial muscle is decreased. These changes decrease atrial muscle conduction velocity. Action potential duration in atrial muscle fibers is prolonged by disopyramide administration. This occurrence increases ERR Postrepolarization refractoriness does not occur with disopyramide, and it appears to differ from quinidine and procainamide in this respect. 

Dofetihde prolongs the plateau phase of the action potential, thereby lengthening the refractory period of the myocardium. The effects on atrial tissue appear to be more profound than those observed in the ventricle. The reason for this is unclear. There is no effect on the voltage-gated sodium channel and as such no effect on the conduction velocity. 

Local anaesthetics slow the rate of rise of the action potential and reduce its height. They also slow impulse conduction and lengthen the refractory period (Figure 5.7). They may elevate the threshold potential but do not affect the RMP. As more and more Na+ channels are blocked by local anaesthetic the value of each successive spike potential gradually decreases to the point where it fails to achieve the value of the threshold potential (Figure 5.7). At this point nerve conduction ceases. 

By blocking sodium channels, procainamide slows the upstroke of the action potential, slows conduction, and prolongs the QRS duration of the ECG. The drug also prolongs the action potential duration by nonspecific blockade of potassium channels. The drug may be somewhat less effective than quinidine (see below) in suppressing abnormal ectopic pacemaker activity but more effective in blocking sodium channels in depolarized cells. 

The effects of digitalis on the electrical properties of the heart are a mixture of direct and autonomic actions. Direct actions on the membranes of cardiac cells follow a well-defined progression an early, brief prolongation of the action potential, followed by shortening (especially the plateau phase). The decrease in action potential duration is probably the result of increased potassium conductance that is caused by increased intracellular calcium (see Chapter 14). All these effects can be observed at therapeutic concentrations in the absence of overt toxicity (Table 13-2). 

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