Conducting tissues, slow current

The slow Ca current in smooth muscle, nodal and conducting tissues. 

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. 

For the most part the selective Class III agents appear to act by inhibition of one or more repolarizing potassiuim currents, especially the delayed rectifier (/k) and/or the inward rectifier (/ki). Less selective agents generally affect sodium currents, as well as potassium currents, which translates to Class I (conduction-slowing) activity. Additional work still needs to be done to increase our understanding of the currents and channels involved in regulation of APD. Care must be taken to evaluate species differences, tissue dif-... 

Class rv drugs block the slow inward Ca current (L-type calcium channel) in cardiac tissue. The most pronounced electrophysiological effects are exerted on cardiac cells that depend on the Ca" " channel for initiating the action potential, such as those found in the sinoatrial and A-V nodes. The administration of class IV drugs slows conduction velocity and increases refractoriness in the A-V node, thereby reducing the ability of the A-V node to conduct rapid impulses to the ventricle. This action may terminate supraventricular tachycardias and can slow conduction during atrial flutter or fibrillation. 

Verapamil blocks both activated and inactivated L-type calcium channels. Thus, its effect is more marked in tissues that fire frequently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current, such as the sinoatrial and atrioventricular nodes. Atrioventricular nodal conduction time and effective refractory period are invariably prolonged by therapeutic concentrations. Verapamil usually slows the sinoatrial node by its direct action, but its hypotensive action may occasionally result in a small reflex increase of sinoatrial nodal rate. 

The Class IV drugs are calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV node (Figure 17.12). Although voltage-sensitive calcium channels occur in many different tissues, the major effect of calcium-channel blockers is on vascular smooth muscle and the heart. 

Ca " is a critical cation necessary for cardiac function in terms of automaticity/ pacemaker activity, conduction of electrical signals, and excitation-contraction coupling of myocytes. Drugs and chemicals that influence Ca flux in cardiac tissue also have a profound effect on the electrical and mechanical function of the heart. The slow Ca " current is mediated, in part, via the voltage-gated L-type Ca channels, one that can be influenced by Ca channel antagonists such as verapamil, D600, and diltiazem. Cardiac toxicity associated with the blockade of this channel can result in the disruption of rhythm and rate, as well as contraction and relaxation, of the heart. 

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