DIFFERENTIAL RESPONSIVENESS OF ATRIAL AND VENTRICULAR MYOCYTES TO POTASSIUM CHANNEL OPENERS

We examined the effects of the potassium channel openers (PCOs) pinacidil and lemakalim (BRL 38227) on action potential (AP) configurations and outward currents in atrial and ventricular myocytes isolated from rabbit and guinea pig hearts, using the whole-cell configuration of the patch clamp technique at 33 degrees-35 degrees C. The PCOs known to activate ATP-sensitive K+ current (I-KATP) in various tissues, induced this current and decreased AP duration (APD) in rabbit ventricular myocytes. In contrast, in rabbit atrial myocytes, PCOs either had no effect or increased duration and plateau amplitude of the AP. The predominant outward current in rabbit atrial myocytes is a 4-aminopyridine (4-AP)-sensitive transient outward current (I-to). The PCOs caused a decrease in I-to without inducing I-KATP in rabbit atria. In identical experimental conditions, PCOs activated I-KATP in both guinea pig atrial and ventricular myocytes. Our results suggest that (a) a species as well as cardiac tissue difference exists in responsiveness to PCOs, and (b) the decrease in I-to without concomitant induction of I-KATP can lead to changes in AP configuration opposite to that expected from I-KATP activation. Different effects of PCOs on distinct parts of the heart could lead to disparity in APD and refractoriness that may contribute to arrhythmogenesis.