Heart action potential

Excitability. Excitabihty refers to electrical responsiveness of the heart to various stimuli by the generation of local excitatory currents, action potentials, or fibrillation. 

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). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

Not all cells in the heart express the fast sodium channel. Thus, sinus nodal and atrioventricular nodal cells lack the fast Na+ channel and instead generate their action potentials via opening of Ca2+ channels. This is the basis for their sensitivity to Ca2+ antagonists. 

Flecainide (Tambocor) and propafenone (Rythmol) are examples of class I-C drags. These drugs have a direct stabilizing action on the myocardium, decreasing the height and rate of rise of cardiac action potentials, thus slowing conduction in all parts of the heart. 

Second, as in the ventricular muscle fibres of the heart, opening of L-type channels can generate sustained plateau potentials following the initial Na +-mediated action potential — for example, in the rhythmically firing neurons of the inferior olive (Fig. 2.7). 

Hayashi, H., Miyata, H., Watanabe, H., Kobayashi A. and Yamazaki, N. (1989). Effects of hydrogen peroxide on action potentials and intracellular Ca concentration of guinea pig heart. Cardiovasc. Res. 23, 767-773. 

Skeletal muscle is neurogenic and requires stimulation from the somatic nervous system to initiate contraction. Because no electrical communication takes place between these cells, each muscle fiber is innervated by a branch of an alpha motor neuron. Cardiac muscle, however, is myogenic, or self-excitatory this muscle spontaneously depolarizes to threshold and generates action potentials without external stimulation. The region of the heart with the fastest rate of inherent depolarization initiates the heart beat and determines the heart rhythm. In normal hearts, this "pacemaker region is the sinoatrial node. 

Parasympathetic stimulation causes a decrease in heart rate. Acetylcholine, which stimulates muscarinic receptors, increases the permeability to potassium. Enhanced K+ ion efflux has a twofold effect. First, the cells become hyperpolarized and therefore the membrane potential is farther away from threshold. Second, the rate of pacemaker depolarization is decreased because the outward movement of K+ ions opposes the effect of the inward movement of Na+ and Ca++ ions. The result of these two effects of potassium efflux is that it takes longer for the SA node to reach threshold and generate an action potential. If the heart beat is generated more slowly, then fewer beats per minute are elicited. 

Verapamil (Class IV antiarrhythmic drug) is an effective agent for atrial or supraventricular tachycardia. A Ca++ channel blocker, it is most potent in tissues where the action potentials depend on calcium currents, including slow-response tissues such as the SA node and the AV node. The effects of verapamil include a decrease in heart rate and in conduction velocity of the electrical impulse through the AV node. The resulting increase in duration of the AV nodal delay, which is illustrated by a lengthening of the PR segment in the ECG, reduces the number of impulses permitted to penetrate to the ventricles to cause contraction. 

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. 

The mechanism of these effects involves enhanced depolarization of these cells due to decreased potassium permeability and increased sodium and calcium permeability. With fewer K+ ions leaving the cell and with more Na+ and Ca++ ions entering the cell, the inside of the cell becomes less negative and approaches threshold more rapidly. In this way, action potentials are generated faster and travel through the conduction pathway more quickly so that the heart can generate more heartbeats per minute (see Figure 14.1). 

Figure 14.1 Effect of autonomic nervous system stimulation on action potentials of the sinoatrial (SA) node. A normal action potential generated by the SA node under resting conditions is represented by the solid line the positive chronotropic effect (increased heart rate) of norepinephrine released from sympathetic nerve fibers is illustrated by the short dashed line and the negative chronotropic effect (decreased heart rate) of acetylcholine released from parasympathetic nerve fibers is illustrated by the long dashed line.

Neurotoxin that preferentially binds to activated sodium channels and increases the intracellular calcium concentration. It prolongs the action potential duration in the heart. It is obtained from sabadilla seeds (Schoenocaulon officinale). Yellowish-white amorphous powder that retains water and melts at 356°F. It is insoluble in water but slightly soluble in ether. Various salts (solids) have been reported. The nitrate is sparingly soluble in water. 

Elliott, A.C., G.L. Smith, and D.G. Allen. 1989. Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide. Circulat. Res. 64 583-591. 

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