Contrasting roles of a novel K+ channel blocker and a K+ channel opener on electro-mechanical activity in canine heart tissue

We tested the effects of a potassium channel opener diazoxide on the action potential duration (APD) and contractile force changes in canine Purkinje tissue induced by a novel class III anti-arrhythmic agent (C3A), KCB-328 (0.5 μM) with 3,4-dimethoxyphenethyl ring structure (0.5 μM). KCB-328 shortened APD25 by 8.3±2.1%, prolonged APD50 and APD90 by 31.2±5.3 and 50.0±7.1%, respectively. Diazoxide (0.1 mM) shortened APD at all levels by 58.3±8.1, 54.1±6.1, and 42.8±5.8%, respectively. In the presence of diazoxide, KCB-328 still prolonged APD50 and APD90 (12.5±3.8 and 26.8±5.9%, respectively). KCB-328 increased force of contraction in a dose-dependent manner. KCB-328 increased force less in the presence of diazoxide. Administration of diazoxide only, reduced force of contraction. We conclude that APD prolongation by KCB-328 may occur even in the presence of diazoxide. It is not sufficient for the restoration of already diminished contractile force and that such an APD prolongation may be unrelated to the restoration of force of contraction even though both are most often seen to occur simultaneously.