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

TitleVolatile anaesthetic effects on phospholipid binding to synaptotagmin 1, a presynaptic Ca2+ sensor.
Publication TypeJournal Article
Year of Publication2005
AuthorsFu D, Vissavajjhala P, Hemmings HC
JournalBr J Anaesth
Date Published2005 Aug
KeywordsAnesthetics, Animals, Calcium, Calcium-Binding Proteins, Genetic Engineering, Halothane, Isoflurane, Isotope Labeling, Liposomes, Membrane Glycoproteins, Nerve Tissue Proteins, Phospholipids, Protein Binding, Protein Structure, Tertiary, Rats, Recombinant Fusion Proteins, Synaptotagmin I, Synaptotagmins

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 Ca(2+)-evoked transmitter release involving critical Ca(2+)/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 Ca(2+) 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 Ca(2+)/phospholipid binding properties of synaptotagmin 1, a Ca(2+) sensor involved in regulating evoked Ca(2+)-dependent neurotransmitter release.

Alternate JournalBr J Anaesth
PubMed ID15923266
Grant ListGM 58055 / GM / NIGMS NIH HHS / United States
GM 61925 / GM / NIGMS NIH HHS / United States