Characterization of a Fast Transient Outward Current in Neocortical Neurons from Epilepsy Patients

Abstract

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 ± 1.8 mV (n = 5) and a slope factor of 17.0 ± 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 ± 8.3 mV (n = 5), with a slope factor of -6.6 ± 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 ± 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 μM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 μM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues. © 2004 Wiley-Liss, Inc.