Volatile anaesthetic effects on phospholipid binding to synaptotagmin 1, a presynaptic Ca2+ sensor.

Abstract

Volatile anaesthetics have important effects on synaptic transmission in the CNS. Depression of excitatory transmission involves reduced transmitter release via unidentified presynaptic mechanisms. Synaptotagmin 1 is a synaptic vesicle-associated protein that regulates Ca(2+)-evoked transmitter release involving critical Ca(2+)/phospholipid interactions within its C2 domains. We analysed the effects of halothane and isoflurane on the binding of purified recombinant rat synaptotagmin 1 C2A, C2B and C2AB domains to radiolabelled phospholipid liposomes. Halothane and isoflurane had no significant effects on the maximal binding or Ca(2+) dependence of binding of synaptotagmin 1 C2 domains to mixed phospholipid vesicles composed of either phosphatidylserine/phosphatidylcholine or phosphatidylinositol/phosphatidylcholine. Inhibition of synaptic vesicle exocytosis by volatile anaesthetics does not appear to involve an effect on the critical Ca(2+)/phospholipid binding properties of synaptotagmin 1, a Ca(2+) sensor involved in regulating evoked Ca(2+)-dependent neurotransmitter release.