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 μA and repolarize the AP with Na(+)-activated K(+) (KNa) 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 ∼ 1.5 mm in anterior-posterior length and ∼ 0.6 mm in diameter, containing ∼ 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 KNa 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 KNa channels is necessary for KNa channel activation. However, our computational simulations showed that KNa channels at a great distance from Na(+) influx can still terminate the AP, suggesting that KNa 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.
Department of Biology, The University of Oklahoma, Norman, Oklahoma; Cellular & Behavioral Neurobiology Graduate Program, The University of Oklahoma, Norman, Oklahoma; and yueban@ou.edu.
Yue
Y
Ban
Samuel Roberts Noble Microscopy Laboratory, The University of Oklahoma, Norman, Oklahoma.
Benjamin E
BE
Smith
Department of Biology, The University of Oklahoma, Norman, Oklahoma; Cellular & Behavioral Neurobiology Graduate Program, The University of Oklahoma, Norman, Oklahoma; and.
Michael R
MR
Markham
D000818:Animals; D001921:Brain / Q000378:metabolism; D003198:Computer Simulation; D004557:Electric Organ / Q000166:cytology* / Q000378:metabolism; D005260:Female; D029941:Fish Proteins / Q000378:metabolism*; D023702:Gymnotiformes / Q000033:anatomy & histology* / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D015221:Potassium Channels / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D029941:Fish Proteins; D015221:Potassium Channels; D015222:Sodium Channels; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
action potential energy efficiency; ion channel compartmentalization; sodium-activated potassium channels; three-dimensional electrolyte morphology