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.