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.