The effects of four general anesthetics on intracellular [Ca2+] in cultured rat hippocampal neurons.
It has been suggested that general anesthesia might arise as a consequence of increased cytoplasmic free ionized calcium concentration ([Ca2+]i). The effect of increased [Ca2+]i might be to activate K+ channels or to modulate other ion channels important for the control of excitability, such as the GABAA receptor. A direct test of this hypothesis has not been reported. Microfluorimetry with the calcium-sensitive dye fura-2 was used to study the effects of four anesthetic agents on the regulation of intracellular free Ca2+ in hippocampal neurons cultured from the embryonic rat hippocampus. Basal intracellular free ionized calcium concentration [Ca2+]i in the neurons was 50-100 nM. Depolarization of the neurons with 50 mM K+ resulted in the elevation of [Ca2+]i to 200-800 nM, with subsequent recovery of [Ca2+]i over several minutes. The volatile anesthetics halothane, enflurane and isoflurane did not alter basal [Ca2+]i, even above clinically relevant concentrations; however, they did inhibit elevation of [Ca2+]i by high K+ stimulation. The intravenous anesthetic methohexital caused small increases in basal [Ca2+]i at concentrations > or = 50 microM; methohexital (5-50 microM) also inhibited elevations of [Ca2+]i induced by high K+. The evidence presented here suggests that the anesthetics studied do not produce their actions via sustained or transient increases in [Ca2+]i. However, all of the anesthetics studied appear to possess inhibitory effects on hippocampal voltage-dependent Ca2+ channels, in addition to their previously described effects at GABAA receptors.
Bleakman
D
D
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
Jones
M V
MV
Harrison
N L
NL
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology; D008723:Methohexital / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000777:Anesthetics; D009553:Nimodipine; D007530:Isoflurane; D008723:Methohexital; D002118:Calcium; D006221:Halothane