HALOTHANE AND ISOFLURANE ALTER CALCIUM DYNAMICS IN RAT CEREBROCORTICAL SYNAPTOSOMES

An increase in synaptosomal Ca2+ triggers neurotransmitter release and volatile anesthetics have been shown to inhibit neurotransmitter rele ase by inhibition of Ca2+ entry. We have examined the effect of isoflu rane and halothane on the kinetics of increase and decrease of Ca2+ in rat cerebrocortical synaptosomes ([Ca2+](in)). We have also used spec ific Ca2+ antagonists to examine the role of L-, N-, and P-type Ca2+ c hannels. Synaptosomal [Ca2+](in) was measured spectrofluorometrically using fura-2 as a Ca2+ reporter; Ca2+ transients were initiated by dep olarization with 40 mM KCI. We found that less than or equal to 1 mini mum alveolar anesthetic concentration halothane and isoflurane decreas ed peak [Ca2+](in) by approximately 40%, that both anesthetics decreas ed the rate of [Ca2+](in) increase and decrease, that specific voltage -dependent calcium channel antagonists had little effect on peak or pl ateau [Ca2+](in), and that the volatile anesthetics increased the perm eability of synaptosomal membranes to Ca2+. These results suggest that the volatile anesthetics, at clinically relevant concentrations, can alter Ca2+ homeostasis in the synapse. Implications: Clinically releva nt concentrations of halothane and isoflurane markedly depress K+-evok ed increases in rat cerebrocortical synaptosomal calcium (Ca2+) unrela ted to L-, N-, and P-type voltage-dependent calcium channels and incre ase the Ca2+ permeability of the synaptosomal membrane. These changes in Ca2+ dynamics could have profound effects on Ca2+ signaling in the synapse.