Properties of the delayed rectifier potassium current in porcine sino-atrial node cells

1. Whole-cell currents were recorded in single, spontaneously active cells dissociated from porcine sino-atrial node, and the conductance and gating properties of the delayed rectifier K+ current (I(K)) were investigated. 2. The isolated cells exhibited spontaneous action potentials at a rate of 80.5 +/- 5.4 min(-1) (mean +/- S.E.M., n = 11). Under Ca2+ current block, (depolarization from -40 mV to various potentials activated a time-dependent outward current (I(K)). The activation curve of I(K) showed a half-activation potential (V1/2) of 20.5 +/- 2.1 mV and a slope factor (S) of 16.4 +/- 1.2 mV (n = 8). 3. As the duration of the depolarizing pulse to either +10 or +60 mV was prolonged, the amplitude of the tail current increased in proportion to that of the activated outward current during depolarization. 4. E4031 (2-5 microM), a selective blocker for the rapidly activating component of I(K) (I(K,r)), hardly affected I(K), but chromanol 293B, a selective blocker for the slowly activating component (I(K,s)), inhibited I(K) with an IC(50) of 8.79 microM. 5. The reversal potential of I(K) was -75.2 +/- 2.3 mV with 5.4 mM external and 150 mM internal K+. The time courses of activation and deactivation of I(K) were fitted by the sum of two exponential functions at various potentials. The relationship between the time constants and membrane potential showed a bell-shaped curve with a peak at around -10 mV for both fast and slow components. 6. The results indicate that in porcine sino-atrial node cells I(K) is largely derived from I(K,s) and that I(K,s) plays a functional role in in the slow diastolic depolarization. I(K,s) may, in part, account for the relatively slower heart rate of pigs than that of rabbit in which I(K,r) is a functionally dominant component of I(K).