Both β-adrenergic receptor stimulation and cardiac tissue type have important roles in elucidating the functional effects of IKs channel blockers in vitro

Abstract

Introduction: Conflicting results associated with the use of I Ks blockers on the action potential duration (APD) have raised a question as to whether the variable results arise from the use of different cardiac tissues, β-adrenergic stimulation, or by the “selectivity” of the chosen I Ks blockers. Methods: We used the highly selective I Ks blocker (−)-[3 R, 4 S] chromanol 293B [(−) chromanol] to mimic drug-induced long QT1 in isolated rabbit Purkinje fibers, papillary muscles, and ventricular trabeculae using the conventional microelectrode technique. Results: I Ks block with (−) chromanol at 1×10 −5 M did not significantly change the APD at different stimulation rates in all three cardiac tissues. Isoproterenol (Iso:1×10 −7 M) shortened APD 90, and (−) chromanol (1×10 −5 M) largely prevented this shortening in isolated papillary muscles at 1 Hz [−3% with Iso combined (−) chromanol group versus −16% with iso group; p<0.05] and also at 2 Hz (+7% versus −25% with Iso group; p<0.05), but did not significantly prevent this shortening in isolated Purkinje fibers. In isolated trabeculae, (−) chromanol combined with Iso significantly prolonged the APD 90 by 15% at 1 Hz (versus −10% with Iso group; p<0.05) and by 5% at 2 Hz (versus −11% with Iso group; p<0.05). Discussion: Our study shows that only during β-adrenoceptor stimulation, pharmacological inhibition of the I Ks current plays an important role in the APD recorded from isolated ventricular trabeculae and papillary muscles, but not from Purkinje fibers. These results indicate that the APD prolonging effects of I Kschannel blockers during β-adrenergic receptor stimulation can only be detected from isolated rabbit papillary muscles and ventricular trabeculae, but not Purkinje fibers.