Electrophysiological Evidence for Increased Calcium-Mediated Potassium Conductance by Low-Dose Sedative-Hypnotic Drugs

  • P. L. Carlen
  • N. Gurevich
  • M. O’Beirne

Abstract

In this chapter evidence is presented favoring the hypothesis that low-dose actions (i. e., mild sedation and anxiolysis) of ethanol, a water-soluble benzodiazepine (midazolam), and pentobarbital are due to enhanced calcium-mediated potassium conductance (Ca-gK). This hypothesis, which developed from results of electrophysiological experiments recording intracellularly from CA1 and CA3 cells in mammalian hippocampal slices, centers around the fact that injection of Ca2+ into excitable cells induces a membrane hyperpolarization by a selective increase in gK [20,24,30,32,33]. Physiologically, Ca-gK is usually triggered by a depolarization-induced influx of Ca2+ from the surrounding medium. On the other hand, persistently raised intracellular free Ca2+ concentration, [Ca2+]i, will actually reduce the depolarization-induced inward Ca2+ current [14,16,20,24,37,43]. However, it was shown in voltage-clamped dorid neurons that the intraneuronal free [Ca2+]i and not the amount of the Ca2+ current is related to the degree of activation of the Ca-gK [15]. Therefore, Ca-gK could be increased even though the inward Ca2+ current is reduced if the source of increased [Ca2+]i is intracellular. The exact way that Ca-gK is activated by a depolarizing current pulse or by injected Ca2+ is unclear. We have used the size of the Ca2+ spikes evoked in neurons perfused with tetrodotoxin (TTX), which blocks Na+-dependent action potentials, as an indirect monitor of the free [Ca2+]i.

Keywords

Permeability Toxicity Acetone Diazepam Midazolam 

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • P. L. Carlen
    • 1
    • 2
  • N. Gurevich
    • 1
    • 2
  • M. O’Beirne
    • 1
    • 2
  1. 1.Addiction Research Foundation Clinical Institute, Playfair Neuroscience UnitToronto Western HospitalTorontoCanada
  2. 2.Departments of Medicine (Neurology), Physiology, and Institute of Medical ScienceUniversity of TorontoTorontoCanada

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