Properties of the Transient Outward Current in Rabbit Sino-atrial Node Cells

Abstract

The electrophysiological properties of the transient outward current were investigated in voltage-clamped single cells from the rabbit sino-atrial node. To make a regional comparison, some experiments were repeated in atrial myocytes. The current–voltage relationship showed a characteristic outward rectification with an activation threshold of −30 mV. External 4-aminopyridine (0.01–5 m M) inhibited this current in a dose-dependent manner (IC50=0.28 m M, Hill coefficient=1.38). The steady-state inactivation exhibited a half-maximum voltage of −35 mV and a slope factor of −.4 mV. The current density of the transient outward current was 6.3±0.5 pA/pF in sino-atrial node cells and 12.3±1.2 pA/pF in atrial cells. The inactivation time constant was faster in sino-atrial node cells (time constants 4.2±0.5 and 26.0±0.6 ms, respectively, for the fast and slow components) than in atrial cells (9.7±1.2 and 44.8±3.2 ms, respectively). Recovery from inactivation was much faster in sino-atrial node cells (time constants 44.7±9.0 ms) than in atrial cells (time constants 1.39±0.32 and 6.70±0.1 s, respectively, for the fast and slow components). These results suggest that the kinetic properties, as well as the current density, of the transient outward current differs between sino-atrial node and atrial cells. Taking the current density of Ito at +10 mV as 2.5±0.3 pA/pF gives a total Ito of approximately 100 pA at the peak of the action potential in rabbit sino-atrial node cells. The action potential duration was increased by 24.8±1.3% by 0.5 m M 4-AP. Thus, Ito may contribute significantly to the repolarization phase in mammalian sino-atrial node cells.