4-Aminopyridine sensitive transient outward current in dog ventricular fibres

(1) The depression of slow inward calcium current (ICa) induced by organic or inorganic inhibitors in voltage clamped dog ventricular preparations unmasks an early transient outward current (Ito). (2) Ito is depressed by 4-aminopyridine (1 mM) in a voltage dependent manner. (3) Ito appears in response to voltage steps above 40 mV (from holding voltage = resting voltage) and increases with raising the amplitude of clamp steps. (4) Within physiological range of membrane voltage Ito is smaller and decays several times faster than ICa. Time course of the decline is approximately exponential (tau = 25 +/- 6 ms at 80 mV above resting voltage). (5) Shifts of the holding voltage by 20 mV from the level of resting voltage alters the peak amplitude of Ito. It is increased by hyperpolarization and reduced by depolarization. (6) The recovery of Ito from inactivation at resting voltage was approximated by a single exponential. Time constant (390 ms) is about 15 times longer than the time constant of inactivation at 80 mV positive to the resting voltage.