Differences between outward currents of human atrial, and subepicardial ventricular myocytes

1. Outward currents were studied in myocytes isolated from human atrial and subepicardial ventricular myocardium using the whole-cell. voltage clamp technique at 22 degrees C. The Na+ current was inactivated with prepulses to -40 mV and the Ca2+ current was eliminated by both reducing extracellular [Ca2+] to 0.5 mM and addition of 100 mu M CdCl2 to the bath solution. 2. In human myocytes, three different outward currents were observed. A slowly inactivating sustained outward current, I-so, was found in atrial but not ventricular myocytes. A rapidly inactivating outward current, I-to, of similar current density was observed in cells from the two tissues. An additional uncharacterized non-inactivating background current of similar size was observed in atrial and in ventricular myocytes. 3. I-to and I-so could be differentiated in atrial myocytes by their different kinetics and potential dependence of inactivation, and their different sensitivities to block by 4-aminopyridine, suggesting that two individual channel types were involved. 4. In atrial cells, inactivation of I-to was more rapid and steady-state inactivation occurred at more negative membrane potentials than in ventricular cells. Furthermore, the recovery of I-to from inactivation was slower and without overshoot in atrial myocytes. In addition, 4-aminopyridine-induced block of I-to was more efficient in atrial than in ventricular cells. These observations suggest that the channels responsible for atrial and ventricular I-to were not identical. 5. We conclude that the differences in outward currents substantially contribute to the particular shapes of human atrial and ventricular action potentials. The existence of I-so in atrial cells only provides a clinically interesting target for anti-arrhythmic drug action, since blockers of I-so would selectively prolong the atrial refractory period, leaving ventricular refractoriness unaltered.