A sodium-activated potassium channel supports high-frequency firing and reduces energetic costs during rapid modulations of action potential amplitude

Abstract

We investigated the ionic mechanisms that allow dynamic regulation of action potential (AP) amplitude as a means of regulating energetic costs of AP signaling. Weakly electric fish generate an electric organ discharge (EOD) by summing the APs of their electric organ cells (electrocytes). Some electric fish increase AP amplitude during active periods or social interactions and decrease AP amplitude when inactive, regulated by melanocortin peptide hormones. This modulates signal amplitude and conserves energy. The gymnotiform Eigenmannia virescens generates EODs at frequencies that can exceed 500 Hz, which is energetically challenging. We examined how E. virescens meets that challenge. E. virescens electrocytes exhibit a voltage-gated Na(+) current (I(Na)) with extremely rapid recovery from inactivation (τ(recov) = 0.3 ms) allowing complete recovery of Na(+) current between APs even in fish with the highest EOD frequencies. Electrocytes also possess an inwardly rectifying K(+) current and a Na(+)-activated K(+) current (I(KNa)), the latter not yet identified in any gymnotiform species. In vitro application of melanocortins increases electrocyte AP amplitude and the magnitudes of all three currents, but increased I(KNa) is a function of enhanced Na(+) influx. Numerical simulations suggest that changing I(Na) magnitude produces corresponding changes in AP amplitude and that K(Na) channels increase AP energy efficiency (10-30% less Na(+) influx/AP) over model cells with only voltage-gated K(+) channels. These findings suggest the possibility that E. virescens reduces the energetic demands of high-frequency APs through rapidly recovering Na(+) channels and the novel use of KNa channels to maximize AP amplitude at a given Na(+) conductance.