The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes: I. Basic characterization and kinetic analysis

Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K⁺ current I_to were quantified. I_to is selective for K⁺, with a P_Na/P_K of 0.082. Activation of I_to is a voltage-dependent process, with both activation and inactivation being independent of Na⁺ or Ca²⁺ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V_1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a sub-threshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I_to channel currents recorded in cell-attached patches reproduce macroscopic I_to and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22°C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half-activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22°C) are rapid, with I_to peaking in ∼5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12°C) demonstrate that activation occurs with a time delay. A nonlinear least-squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22°C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, I_to gating can be described using an a ³i formulation.