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.
Mishima
Tatsuya
T
Department of Physiology, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan. mishimat@kyorin-u.ac.jp
Fujiwara
Tomonori
T
Akagawa
Kimio
K
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D051381:Rats; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000378:metabolism; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins