ISOFLURANE REDUCES SYNAPTIC GLUTAMATE RELEASE WITHOUT CHANGING CYTOSOLIC-FREE CALCIUM IN ISOLATED NERVE-TERMINALS

The molecular mechanism of volatile anaesthetic action on presynaptic glutamate release is not clear. An inhibitory effect on voltage-gated calcium channels has been proposed. The present study examines the eff ect of isoflurane on cytosolic free calcium and synaptic glutamate rel ease from isolated nerve terminals. Synaptosomes from rat cerebral cor tex were used. Glutamate was measured with a continuous fluorometric m easurement in a spectrophotometer as the fluorescence of NADPH and cal cium as the fluorescence of fura-2. Isoflurane reduced the calcium-dep endent glutamate release evoked by membrane depolarization with 4-amin opyridine in an inversely dose-dependent manner. The glutamate release was reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%, respectively (for all: P<0.05), Membrane depolarization evoked a rise in cytosolic free calcium of approximate to 34%. Addition of iso flurane (0.5, 1.5 and 3.0%) produced no significant change in cytosoli c free calcium. These results indicate that the isoflurane-induced red uction in presynaptic glutamate release is caused by other mechanisms than blocking voltage-gated calcium channels. As the release is invers ely dose-dependent, two or more mechanisms could be involved.