Distribution of I to or I K1 or I K
channels in heart is significantly different in species and
tissues. Three subtypes of I K channels, I Kur , I Kr and I Ks have been identified at least. Most
blockers of I to , I K1 and I K produce positive inotropic and negative chronotropic effects in the heart. In contrast to class Ⅰ
antiarrhythmic agents, I Kr blockers selectively modulate electrophysiological responses to parasympathetic nerve stimulation. I to blockers increase atrial action potential duration selectively, the prolongation by I K blockers of atrial and ventricular effective refractory period in mammalian is different. Reverse use dependence is the main shortage of class Ⅲ antiarrhythmic agents (blockade of I Kr ) used clinically, which may be related to an accumulation of I Ks current at high heart rate. Application of class Ⅲ antiarrhythmic agents together with I Ks blockers or β adrenergic antagonists may increase their therapeutic effects, and decrease the occurrence of TdP.