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Dual and opposing roles of presynaptic Ca²⁺ influx for spontaneous GABA release from rat medial preoptic nerve terminals

Michael Druzin *†, David Haage *, Evgenya Malinina *† and Staffan Johansson *

Calcium influx into the presynaptic nerve terminal is well established as a trigger signal for transmitter release by exocytosis. By studying dissociated preoptic neurons with functional adhering nerve terminals, we here show that presynaptic Ca²⁺ influx plays dual and opposing roles in the control of spontaneous transmitter release. Thus, application of various Ca²⁺ channel blockers paradoxically increased the frequency of spontaneous (miniature) inhibitory GABA-mediated postsynaptic currents (mIPSCs). Similar effects on mIPSC frequency were recorded upon washout of Cd²⁺ or EGTA from the external solution. The results are explained by a model with parallel Ca²⁺ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca²⁺-activated K⁺ channels at a distance from the release site.

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