Modulatory effects of gamma-hydroxybutyric acid on a GABA(A) receptor from crayfish muscle.
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.
Physiologisches Institut der Technischen Universität München, Germany. adelsberger@physiol.med.tu-muenchen.de
H
H
Adelsberger
S
S
Brunswieck
J
J
Dudel
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000187:drug effects*; D012978:Sodium Oxybate / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018118:Chloride Channels; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate