THE EFFECTS OF 4 GENERAL-ANESTHETICS ON INTRACELLULAR [CA2-NEURONS(] IN CULTURED RAT HIPPOCAMPAL)

It has been suggested that general anesthesia might arise as a consequ ence of increased cytoplasmic free ionized calcium concentration {[Ca2 +](i)}. The effect of increased [Ca2+](i) might be to activate K+ chan nels or to modulate other ion channels important for the control of ex citability, such as the GABA(A) receptor. A direct test of this hypoth esis has not been reported. Microfluorimetry with the calcium-sensitiv e dye fura-2 was used to study the effects of four anesthetic agents o n the regulation of intracellular free Ca2+ in hippocampal neurons cul tured from the embryonic rat hippocampus. Basal intracellular free ion ized calcium concentration [Ca2+](i) in the neurons was 50-100 nM. Dep olarization 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 se veral minutes. The volatile anesthetics halothane, enflurane and isofl urane did not alter basal [Ca2+](i), even above clinically relevant co ncentrations; 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 greater than or equal t o 50 mu M; methohexital (5-50 mu M) 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 tra nsient 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 G ABA(A) receptors.