Complete and reversible block by omega-grammotoxin SIA of glutamatergic synaptic transmission between cultured rat hippocampal neurons.
omega-Grammotoxin SIA (omega-GsTx SIA), a peptide isolated from tarantula venom, inhibits synaptosomal Ca2+ influx and neurotransmitter release, and blocks N-, P-, and Q-type voltage-gated Ca2+ channels. The whole-cell patch-clamp was used to record glutamatergic excitatory post-synaptic currents (EPSCs) evoked by extracellular stimulation of presynaptic neurons in primary rat hippocampal cultures. EPSCs displayed rapid kinetics and were blocked by CNQX. omega-Conotoxin (1 microM) GVIA inhibited EPSCs by 46%, while 30 nM and 1 microM omega-agatoxin IVA produced 12% and 69% inhibition, respectively, consistent with coupling of N-, P- and Q-type Ca2+ channels to glutamatergic synaptic transmission. omega-GsTx SIA (1 microM) rapidly, completely, and reversibly blocked glutamatergic EPSCs, but did not affect currents evoked by bath application of kainate. Thus, omega-GsTx SIA blocks glutamatergic synaptic transmission by blocking presynaptic voltage-gated Ca2+ channels. omega-GsTx SIA is the only agent that blocks selectively and reversibly the Ca2+ channels coupled to glutamate release. omega-GsTx SIA provides a unique and powerful tool for experiments requiring recovery of function following presynaptic block of synaptic transmission.
Piser
T M
TM
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455, USA.
Lampe
R A
RA
Keith
R A
RA
Thayer
S A
SA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology* / Q000502:physiology; D006207:Half-Life; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; C082807:omega-grammotoxin SIA; D018698:Glutamic Acid