RT Journal Article SR Electronic T1 Spike-frequency dependent coregulation of multiple ionic conductances in fast-spiking cells forces a metabolic tradeoff JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.08.434486 DO 10.1101/2021.03.08.434486 A1 Yue Ban A1 Rosalie Maltby A1 Michael R. Markham YR 2021 UL http://biorxiv.org/content/early/2021/03/09/2021.03.08.434486.abstract AB High-frequency action potentials (APs) allow rapid information acquisition and processing in neural systems, but create biophysical and metabolic challenges for excitable cells. The electric fish Eigenmannia virescens images its world and communicates with high-frequency (200-600 Hz) electric organ discharges (EODs) produced by synchronized APs generated at the same frequency in the electric organ cells (electrocytes). We cloned three previously unidentified Na+-activated K+ channel isoforms from electroctyes (eSlack1, eSlack2, and eSlick1). In electrocytes, mRNA transcript levels of the rapidly-activating eSlick, but not the slower eSlack1 or eSlack2, correlated with EOD frequency across individuals. In addition, transcript levels of an inward-rectifier K+ channel, a voltage-gated Na+ channel, and Na+,K+-ATPases also correlated with EOD frequency while a second Na+ channel isoform did not. Computational simulations showed that maintaining electrocyte AP waveform integrity as firing rates increase requires scaling conductances in accordance with these mRNA expression correlations, causing AP metabolic costs to increase exponentially.Competing Interest StatementThe authors have declared no competing interest.