title: Halothane enhances tonic neuronal inhibition by elevating intracellular calcium.
abstract: Whether the major action of anesthetics is to depress the central nervous system (CNS) by reducing excitation or enhancing inhibition remains unknown. Using whole cell patch-clamp recording in hippocampal slices, halothane and pentobarbital were found to prolong the decay time constant (TAU(D)) of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). Intracellular administration of the Ca2+ chelator BAPTA or the Ca2+ release inhibitor dantrolene significantly (ANOVA, P less than 0.005) reduced halothane's effect; in contrast, the pentobarbital effect was unchanged. Halothane induced depression of population spike amplitude was blocked by the GABAA antagonist bicuculline. Together, these findings suggest that a major depressant effect of halothane involves enhancement of GABAA-mediated inhibition through release of intraneuronally stored Ca2+.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.
authors.forename: I
authors.initials: I
authors.lastname: Mody
authors.forename: D L
authors.initials: DL
authors.lastname: Tanelian
authors.forename: M B
authors.initials: MB
authors.lastname: MacIver
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D005071:Evoked Potentials / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000166:cytology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology
chemical_list: D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D003620:Dantrolene; D010424:Pentobarbital; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D006221:Halothane; D001640:Bicuculline