Modulatory effects of gamma-hydroxybutyric acid on a GABA(A) receptor from crayfish muscle

Eur J Pharmacol. 1998 Jun 5;350(2-3):317-23. doi: 10.1016/s0014-2999(98)00252-0.

Abstract

The effects of gamma-hydroxybutyric acid (GHB) were evaluated with a gamma-aminobutyric acid (GABA) activated Cl- channel on crayfish deep extensor abdominal muscle. GABA and GHB were applied to outside-out patches using a fast application system. Application of GHB up to 10 mM did not result in detectable activation of the channel. After coapplication of GABA and GHB, a dose-dependent potentiation of the GABA-elicited current by GHB was observed. The maximal effect was obtained with 0.5-1 mM GHB, with which the amplitude was enhanced by about 50% with 0.4 or 1 mM GABA. Simultaneously with the potentiating effect, a decrease of the rise times was seen. Preapplication of GHB, prior to the GABA pulses, resulted in a reduction of the current amplitude elicited by GABA. This block was persistent throughout the application time of GABA. Therefore, two contrasting effects of GHB on this chloride channel, a potentiating one and a blocking one, seemed to occur simultaneously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Astacoidea / physiology*
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • GABA Agonists / pharmacology
  • GABA-A Receptor Agonists
  • In Vitro Techniques
  • Kinetics
  • Membrane Potentials / drug effects
  • Muscles / drug effects
  • Muscles / metabolism*
  • Patch-Clamp Techniques
  • Receptors, GABA-A / drug effects*
  • Sodium Oxybate / pharmacology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Anesthetics, Intravenous
  • Chloride Channels
  • GABA Agonists
  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Sodium Oxybate