Volatile anaesthetic effects on phospholipid binding to synaptotagmin 1, a presynaptic Ca2+ sensor.
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.
Fu
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Department of Anesthesiology, Weill Medical College of Cornell University, New York, NY, USA.
Vissavajjhala
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Hemmings
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HC
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005818:Genetic Engineering; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D007553:Isotope Labeling; D008081:Liposomes; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins
D000777:Anesthetics; D002135:Calcium-Binding Proteins; D008081:Liposomes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D050857:Synaptotagmins; D007530:Isoflurane; D002118:Calcium; D006221:Halothane