DIFFERENTIAL RESPONSIVENESS OF ATRIAL AND VENTRICULAR MYOCYTES TO POTASSIUM CHANNEL OPENERS

We examined the effects of the potassium channel openers (PCOs) pinaci dil 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 th e 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 my ocytes. In contrast, in rabbit atrial myocytes, PCOs either had no eff ect or increased duration and plateau amplitude of the AP. The predomi nant outward current in rabbit atrial myocytes is a 4-aminopyridine (4 -AP)-sensitive transient outward current (I-to). The PCOs caused a dec rease in I-to without inducing I-KATP in rabbit atria. In identical ex perimental conditions, PCOs activated I-KATP in both guinea pig atrial and ventricular myocytes. Our results suggest that (a) a species as w ell 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-K ATP activation. Different effects of PCOs on distinct parts of the hea rt could lead to disparity in APD and refractoriness that may contribu te to arrhythmogenesis.