Ion channels and cardiac arrhythmias

Changes in ionic currents through ion channels of the myocardial cell membrane have to be regarded as main cause of cardiac arrhythmias. Three basic arrhythmogenic mechanisms are responsible for the initiation oft tachyarrhythmias: 1. The disturbance of normal automaticity in cardiac pacemaker cells dependent on the currents I-f, ICa-L, I-Ca,I-T or I-K-ACh,I-Ado and the occurrence of abnormal automaticity in atrial and ventricular working myocardium based on the currents ICa-L, I-Na, I-K, I-Kl or I-K-ACh,I-Ado. 2. Triggered activity which may be recognized by the appearance of early (EAD) or late afterdepolarizations (LAD). EAD are mainly due to inhibition of the outward currents I-Kr and I-Ks and are favoured by an increase in the inward currents I-Na and ICa-L, respectively. Typical arrhythmias are torsade de pointes occurring during treatment with K+-channel inhibitors(e.g. sotalol) or in patients with QT-syndrome. LAD may be observed during Ca2+-overload of the myocardial cell (digitalis intoxication, catecholamines) and are based on the transient inward current I-ti, which is build up by the participation of the currents I-Na/Ca, I-NS and ICa-L. 3. Reentry mechanisms are the most frequent cause of tachyarrhythmias. They originate in an anatomically defined excitation circle with unidirectional block. Na+- and Ca2+-channel dependent disturbances of conduction with long excitable gap may be distinguished from Na+-channel dependent disturbances of conduction and refractory period with short excitable gap. Interruption of reentry is possible in the first case by depression of conduction and excitability (Na+- or Ca2+-channel blockers), in the second case by increase in refractory period (K+- or Na+-channel blockers).