A highly polarized excitable cell separates sodium channels from sodium-activated potassium channels by more than a millimeter

The bioelectrical properties and resulting metabolic demands of electrogenic cells are determined by their morphology and the subcellular localization of ion channels. The electric organ cells (electrocytes) of the electric fish Eigenmannia virescens generate action potentials (APs) with Na+ currents > 10 mu A and repolarize the AP with Na+-activated K+ (K-Na) channels. To better understand the role of morphology and ion channel localization in determining the metabolic cost of electrocyte APs, we used two-photon three-dimensional imaging to determine the fine cellular morphology and immunohistochemistry to localize the electrocytes' ion channels, ionotropic receptors, and Na+-K+-ATPases. We found that electrocytes are highly polarized cells similar to 1.5 mm in anterior-posterior length and similar to 0.6 mm in diameter, containing similar to 30,000 nuclei along the cell periphery. The cell's innervated posterior region is deeply invaginated and vascularized with complex ultrastructural features, whereas the anterior region is relatively smooth. Cholinergic receptors and Na+ channels are restricted to the innervated posterior region, whereas inward rectifier K+ channels and the K-Na channels that terminate the electrocyte AP are localized to the anterior region, separated by > 1 mm from the only sources of Na+ influx. In other systems, submicrometer spatial coupling of Na+ and K-Na channels is necessary for K-Na channel activation. However, our computational simulations showed that K-Na channels at a great distance from Na+ influx can still terminate the AP, suggesting that K-Na channels can be activated by distant sources of Na+ influx and overturning a long-standing assumption that AP-generating ion channels are restricted to the electrocyte's posterior face.