A-type Potassium Currents Active at Subthreshold Potentials in Mouse Cerebellar Purkinje Cells

Voltage-dependent and calcium-independent K+ currents were whole-cell recorded from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mM) application isolated an A-type K+ current (I(K(A))) with a peak amplitude, at +20 mV, of about one third of the total voltage-dependent and calcium-independent K+ current. The I(K(A)) activated at about -60 mV, had a V(0.5) of activation of -24.9 mV and a V(0.5) of inactivation of -69.2 mV. The deactivation time constant at -70 mV was 3.4 +/- 0.4 ms, while the activation time constant at +20 mV was 0.9 +/- 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two time constants; those at +20 mV were 19.3 +/- 3.1 and 97.6 +/- 9.8 ms. The recovery from inactivation had two time constants of 60.8 ms (78.4 %) and 962.3 ms (21.6 %). The I(K(A)) was blocked by 4-aminopyridine with an IC50 of 67.6 microM. Agitoxin-2 (2 nM) blocked 17.4 +/- 2.1 % of the I(K(A)). Flecainide completely blocked the I(K(A)) with a biphasic effect with IC50 values of 4.4 and 183.2 microM. In current-clamp recordings the duration of evoked action potentials was affected neither by agitoxin-2 (2 nM) nor by flecainide (3 microM), but action potentials that were already broadened by TEA were further prolonged by 4-aminopyridine (100 microM). The amplitude of the hyperpolarisation at the end of depolarising steps was reduced by all these blockers.