Evidence for a Slowly Inactivating K+ Current in Prefrontal Cortical Cells

The in vitro slice preparation of rat prefrontal cortical cells was used to analyse the presence and characteristics of a slowly inactivating outward current and its effect on the delayed integration of synaptic inputs. Pyramidal cells were identified as regular firing or bursting cells. In a fraction of these cells a depolarizing current pulse to -40 mV from a holding potential of -95 mV evoked the fast outward IA current followed by a slower outward current (IKs) which inactivated slowly during the 3-s pulse. This slowly inactivating outward current was completely inactivated at holding potentials near -40 mV and was fully deinactivated by large hyperpolarizing pulses of 1 s duration. It was sensitive to micromolar concentrations of 4-aminopyridine and to 10 mM tetraethylammonium. In current clamp experiments, when the cells were maintained at -80 mV, they responded to subliminal depolarizing current pulses by a slow rising depolarization which reached threshold for spike firing after a delay of several seconds. This delay was considerably reduced either by maintaining the cell at less hyperpolarized potentials or by bath application of 40 microM 4-aminopyridine, or by repeated application of depolarizing pulses. The inactivation of IKs by the last procedure also led to plateau depolarization of the cell. These results suggest that the activation of the slowly inactivating outward current IKs can shunt excitatory inputs, preventing the cell from reaching spike threshold as long as it is not largely inactivated.