Gamma-hydroxybutyrate promotes oscillatory activity of rat and cat thalamocortical neurons by a tonic GABAB, receptor-mediated hyperpolarization.
The actions of gamma-hydroxybutyrate, a drug known to lead to an increase in nocturnal slow wave sleep and induce epileptic states following systemic application, on the membrane properties of thalamocortical neurons from brain slices of the rat and cat dorsal lateral geniculate nucleus were studied using sharp electrode intracellular recordings. Gamma-hydroxybutyrate applied by addition to the perfusion medium led to a concentration-dependent and reversible hyperpolarization of the membrane potential accompanied by a decrease in apparent input resistance (0.1 mM: 2.3 +/- 0.3 mV, 9.5 +/- 1.0%; 10 mM: 11.3 +/- 1.3 mV, 37.5 +/- 10.8%, respectively). In six of seven neurons the iontophoretic or bath (0.1-0.2 mM) application of low concentrations of gamma-hydroxybutyrate led to a hyperpolarization accompanied by the appearance of low-frequency (< 4 Hz) membrane potential oscillations crowned by bursts of action potentials, when the membrane potential of these neurons was initially set depolarized to the range where ongoing oscillatory activity occurred. The gamma-hydroxybutyrate-elicited hyperpolarization was reversibly antagonized by the co-application of the GABAB receptor antagonist CGP 35348 (0.4-1 mM), but was not affected by the putative gamma-hydroxybutyrate receptor antagonist NCS 382 (0.1-5 mM) or tetrodotoxin (1 microM), suggesting that gamma-hydroxybutyrate tonically activates postsynaptic GABAB receptors. The gamma-hydroxybutyrate-induced promotion of oscillatory activity and action potential burst firing of thalamocortical neurons may be one mechanism by which gamma-hydroxybutyrate leads to an increase in the deep stages of sleep and the generation of electroencephalogram and behavioural patterns typical of absence epilepsy.
Williams
S R
SR
Department of Physiology, University of Wales College of Cardiff, U.K.
Turner
J P
JP
Crunelli
V
V
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D058788:GABA-B Receptor Antagonists; D005829:Geniculate Bodies / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects; D012978:Sodium Oxybate / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000166:cytology* / Q000187:drug effects
D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D013779:Tetrodotoxin; D012978:Sodium Oxybate; C066430:CGP 35348