Sodium-activated potassium channels are functionally coupled to persistent sodium currents

We report a novel coupled system of sodium-activated potassium currents (I _KNa) and persistent sodium currents (I _NaP), the components of which are widely distributed throughout the brain. Its existence and importance has not been previously recognized. Although I _KNa was known to exist in many cell types, the source of Na ⁺which activates I _KNa remained a mystery. We now show in single membrane patches generated from the somas of rat neurons that sodium influx through I _NaP is sufficient for activation of K _Na channels, without substantial contribution from the transient sodium current or bulk [Na ⁺] _i. I _NaP was found to be active at cell membrane resting potentials, a finding that may explain why I _KNa can be evoked from negative holding potentials. These results show an unanticipated role for I _NaP in activating a negative feedback system countering the excitable effects I _NaP the interrelatedness of I _NaP and I _KNa suggests new ways neurons can tune their excitability.