Cardiac action potential conduction

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. 

Other potassium channels also play important roles here. For example, Kv4.3/ KChIP complex conducts the transient outward current, Ito, responsible for the descending phase 1 of the cardiac action potential, whereas Kvl.5 is underlying the ultra rapid delayed rectifying current, IKur, responsible for descending phase 2. Finally, inward rectifier potassium channel (Kir2 family) is responsible for IKl current, which maintains the action potential close to or at the resting level (phase 4). 

Local anaesthetics directly depress myocardial conduction and contractility in a dose-dependent manner. They bind to and inactivate myocardial sodium channels, reducing the velocity of the cardiac action potential and prolonging the QRS interval. As plasma concentrations approach toxic values sodium channels become progressively inactivated until there is a generalised reduction in automaticity (cardiac slowing) with negative inotropy. Slow increases to near- or above-toxic levels are better tolerated than rapid rises seen following intravascular injection. 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

The cardiac action potential is normally conducted throughout the heart in a coordinated and predictable pattern (Fig. 2 3-2).5 The action potential originates in the SA node and is conducted throughout both atria via the atrial muscle cells. While spreading through the atria, the action potential reaches the AV node. From the AV node, the action potential... 

Class IV drugs have a selective ability to block calcium entry into myocardial and vascular smooth-muscle cells. These drugs inhibit calcium influx by binding to specific channels in the cell membrane.12,15 As discussed previously, calcium entry plays an important role in the generation of the cardiac action potential, especially during phase 2. By inhibiting calcium influx into myocardial cells, calcium channel blockers can alter the excitability and conduction of cardiac tissues. 

Bupivacaine has a potent depressant effect on electrical conduction in the heart, primarily via an action on voltage-gated sodium channels that govern the initial rapid depolarization of the cardiac action potential. 

The systemic hemodynamic actions of nicorandil are occasionally associated with a transient increase in heart rate of up to 18% (9,10). Larger doses are associated with cardiac depression, a dose-dependent fall in sinus rate and atrioventricular conduction velocity (11), and shortening of the cardiac action potential duration (12). However, no prodysrhythmic effects have been observed in man (13,14). Single oral doses over 40 mg have been associated with severe postural hypotension, dizziness, and syncope (10,15). 

The p adrenoceptor antagonists (beta blockers) are class II antiarrhythmic agents. They prolong phase 4 of the cardiac action potential (pacemaker potential), slowing the heart rate. There are three subtypes of P adrenoceptors Pi, P2 and P3. Stimulation of Pi adrenoceptors in the heart increases the force and rate of cardiac contraction, as well as increasing automaticity of the pacemaker sites and conduction through the AV node. The P2... 

The cardiac action potential can be divided into five phases, numbered 0-4. These phases result from the subsequent or parallel activity of ion channels (Figure 3.2) and/or transporters. Initially, the cell is polarized to near the electrochemical potential for potassium ions because of high K+ conductance at rest. A rapid depolarization is initiated by the activation of the fast inward Na+ current (phase 0). This depolarization is followed by a brief partial repolarization mainly resulting from the activation of the transient outward current (/t0) and the inactivation... 

It is established that Ca + and K+ are involved in maintenance and termination of the plateau phase of the cardiac action potential. Furthermore, intracellular calcium concentration controls membrane K+ permeability via the various conductance components for K+ (gK], gK2, glx) (69) It is also established that action potential duration and myocardial tension development are integrally related (13). In view of previous observations and explanations for the excitation-contraction coupling process and the effects of calcium inhibitory compounds upon the cardiac action potential of ventricular muscle and Purkinje fibers, one possible explanation for the effects observed in ventricular muscle preparations is that low concentrations of calcium inhibitory compounds reduce the amount of intracellular free calcium in the vicinity of the K+ channel, thereby changing the channel s configuration resulting in a reduction in gK+ and delayed repolarization of the ventricular muscle action potential. 

Electrophysiological studies have demonstrated that CN causes a marked shortening of cardiac action potentials. This shortening can be counteracted by glucose, and is due to a marked increase in K+ conductance (Van der Heyden et al., 1985). Dogs dosed with iv CN (2.5 mg kg-1) had an initial decrease in arterial blood pressure, hyperventilation, increased central venous pressure and bradycardia (Vick and Froehlich, 1985). This was followed by respiratory paralysis and increased blood pressure, and then by terminal apnoea, progressive hypotension, profound bradycardia and hypoxic ECG changes. 

Nifedipine, like other dihydropyridines. does not have an appreciable effect on cardiac tissue or conduction. Therefore, there is limited effect on the cardiac action potential. 

Magnesium has been shown to affect the conduction of both sodium and potassium in the heart, which may be due, at least in part, to the dependence of cardiac adenosinetriphosphatase (ATPase) on magnesium. It also competes with calcium and thus decreases calcium conductance across the cardiac membranes, resulting in a prolongation of phase II of the cardiac action potential. Given intravenously, it has been shown to decrease digitalis-induced arrhythmias and torsades de pointes in susceptible patients, as well as arrhythmias produced by myocardial ischemia (e.g., due to infarction). 

These drugs decrease the rate of conduction in the AV node, due to the changes in the cardiac action potential as discussed above (increased effective refractory period [ERP1). 

---