Reduction of neurotransmitter release by the exogenous H3 domain peptide of HPC-1/syntaxin 1A in cultured rat hippocampal neurons.

The membrane protein HPC-1/syntaxin 1A plays a key role in synaptic vesicle exocytosis in the presynaptic terminal. In particular, the H3 domain of HPC-1/syntaxin 1A participates in several protein-protein interactions that regulate neurotransmitter release. To investigate H3 domain function in neurotransmitter release, we used paired whole-cell patch clamping to record the evoked inhibitory postsynaptic currents in cultured hippocampal neurons. Introducing H3 domain peptide into the presynaptic neuron with a patch electrode depressed neurotransmitter release in a stimulation-frequency-dependent manner. Recovery from synaptic vesicle depletion induced by tetanic stimulation was significantly slowed by exogenous H3 domain peptide. These results suggest that the H3 domain peptide reduces neurotransmitter release by retarding the refilling of readily releasable vesicles.