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

Abstract

Background. 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 Ca2+-evoked transmitter release involving critical Ca2+/phospholipid interactions within its C2 domains. Methods. 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. Results. Halothane and isoflurane had no significant effects on the maximal binding or Ca2+ dependence of binding of synaptotagmin 1 C2 domains to mixed phospholipid vesicles composed of either phosphatidylserine/phosphatidylcholine or phosphatidylinositol/ phosphatidylcholine. Conclusions. Inhibition of synaptic vesicle exocytosis by volatile anaesthetics does not appear to involve an effect on the critical Ca2+/phospholipid binding properties of synaptotagmin 1, a Ca2+ sensor involved in regulating evoked Ca2+ -dependent neurotransmitter release. © The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved.