Differential changes of potassium currents in CA1 pyramidal neurons after transient forebrain ischemia

J Neurophysiol. 2000 Dec;84(6):2834-43. doi: 10.1152/jn.2000.84.6.2834.

Abstract

CA1 pyramidal neurons are highly vulnerable to transient cerebral ischemia. In vivo studies have shown that the excitability of CA1 neurons progressively decreased following reperfusion. To reveal the mechanisms underlying the postischemic excitability change, total potassium current, transient potassium current, and delayed rectifier potassium current in CA1 neurons were studied in hippocampal slices prepared before ischemia and at different time points following reperfusion. Consistent with previous in vivo studies, the excitability of CA1 neurons decreased in brain slices prepared at 14 h following transient forebrain ischemia. The amplitude of total potassium current in CA1 neurons increased approximately 30% following reperfusion. The steady-state activation curve of total potassium current progressively shifted in the hyperpolarizing direction with a transient recovery at 18 h after ischemia. For transient potassium current, the amplitude was transiently increased approximately 30% at approximately 12 h after reperfusion and returned to control levels at later time points. The steady-state activation curve also shifted approximately 20 mV in the hyperpolarizing direction, and the time constant of removal of inactivation markedly increased at 12 h after reperfusion. For delayed rectifier potassium current, the amplitude significantly increased and the steady-state activation curve shifted in the hyperpolarizing direction at 36 h after reperfusion. No significant change in inactivation kinetics was observed in the above potassium currents following reperfusion. The present study demonstrates the differential changes of potassium currents in CA1 neurons after reperfusion. The increase of transient potassium current in the early phase of reperfusion may be responsible for the decrease of excitability, while the increase of delayed rectifier potassium current in the late phase of reperfusion may be associated with the postischemic cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Delayed Rectifier Potassium Channels
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • In Vitro Techniques
  • Ischemic Attack, Transient / metabolism*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Potassium / metabolism*
  • Potassium Channel Blockers
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Prosencephalon / blood supply*
  • Prosencephalon / pathology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Tetraethylammonium / pharmacology

Substances

  • Delayed Rectifier Potassium Channels
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Tetraethylammonium
  • 4-Aminopyridine
  • Potassium