Two components of the delayed rectifier potassium current, I-K, in rabbit sino-atrial node cells

The delayed rectifier current was studied in rabbit isolated sino-atrial (SA) node cells using the whole-cell voltage damp technique with amphotericin-permeabilized patches. The envelope of tails test indicated that in SA node cells the decay of I-K(I-K,I-tail) comprises two distinct current components similar to the specific fast and slow components of I-K(I-Kr and I-Ks) that have been found in atrial and ventricular myocytes. Dofetilide, a Class III antiarrhythmic agent and a selective blocker of I-Kr, separated the delayed rectifier current into drug-sensitive current (I-Ks) and drug-insensitive current (I-Ks). The dofetilide-sensitive current activated rapidly and it showed two components of deactivation, the larger of which was very slow, while the dofetilide-insensitive current activated more slowly and deactivated quickly. The effects of propofol, an I-Ks blocker, on the delayed rectifier current were also investigated. The results show that I-Ks contributes to I-K,I-tail and that the more positive the membrane potential, the more the contribution of I-Ks. The ratio of I-Ks to I-Kr in tail currents al -40 mV after a 1 s clamp pulse to +40 mV was 0.3-0.4:1. Dofetilide slowed spontaneous activity, suggesting that I-Kr contributes to the pacemaker activity of the SA node cell.