Chemical anoxia activates ATP-sensitive and blocks Ca(2+)-dependent K(+) channels in rat dorsal vagal neurons in situ

Neuroscience. 2002;110(3):541-54. doi: 10.1016/s0306-4522(01)00468-7.

Abstract

The contribution of subclasses of K(+) channels to the response of mammalian neurons to anoxia is not yet clear. We investigated the role of ATP-sensitive (K(ATP)) and Ca(2+)-activated K(+) currents (small conductance, SK, big conductance, BK) in mediating the effects of chemical anoxia by cyanide, as determined by electrophysiological analysis and fluorometric Ca(2+) measurements in dorsal vagal neurons of rat brainstem slices. The cyanide-evoked persistent outward current was abolished by the K(ATP) channel blocker tolbutamide, but not changed by the SK and BK channel blockers apamin or tetraethylammonium. The K(+) channel blockers also revealed that ongoing activation of K(ATP) and SK channels counteracts a tonic, spike-related rise in intracellular Ca(2+) ([Ca(2+)](i)) under normoxic conditions, but did not modify the rise of [Ca(2+)](i) associated with the cyanide-induced outward current. Cyanide depressed the SK channel-mediated afterhyperpolarizing current without changing the depolarization-induced [Ca(2+)](i) transient, but did not affect spike duration that is determined by BK channels. The afterhyperpolarizing current and the concomitant [Ca(2+)](i) rise were abolished by Ca(2+)-free superfusate that changed neither the cyanide-induced outward current nor the associated [Ca(2+)](i) increase. Intracellular BAPTA for Ca(2+) chelation blocked the afterhyperpolarizing current and the accompanying [Ca(2+)](i) increase, but had no effect on the cyanide-induced outward current although the associated [Ca(2+)](i) increase was noticeably attenuated. Reproducing the cyanide-evoked [Ca(2+)](i) transient with the Ca(2+) pump blocker cyclopiazonic acid did not evoke an outward current. Our results show that anoxia mediates a persistent hyperpolarization due to activation of K(ATP) channels, blocks SK channels and has no effect on BK channels, and that the anoxic rise of [Ca(2+)](i) does not interfere with the activity of these K(+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Apamin / pharmacology
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Chelating Agents / pharmacology
  • Cyanides / pharmacology
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Female
  • Hypoglycemic Agents / pharmacology
  • Hypoxia, Brain / metabolism*
  • Hypoxia, Brain / physiopathology
  • KATP Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / metabolism*
  • Potassium Channels, Inwardly Rectifying
  • Rats
  • Rats, Wistar
  • Small-Conductance Calcium-Activated Potassium Channels
  • Tetraethylammonium / pharmacology
  • Tolbutamide / pharmacology
  • Vagus Nerve / cytology
  • Vagus Nerve / drug effects
  • Vagus Nerve / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Chelating Agents
  • Cyanides
  • Hypoglycemic Agents
  • KATP Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Inwardly Rectifying
  • Small-Conductance Calcium-Activated Potassium Channels
  • uK-ATP-1 potassium channel
  • Apamin
  • Tetraethylammonium
  • Tolbutamide
  • Calcium