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 tarant ula venom, inhibits synaptosomal Ca2+ influx and neurotransmitter rele ase, and blocks N-, P-, and Q-type voltage-gated Ca2+ channels. The wh ole-cell patch-clamp was used to record glutamatergic excitatory post- synaptic currents (EPSCs) evoked by extracellular stimulation of presy naptic neurons in primary rat hippocampal cultures. EPSCs displayed ra pid kinetics and were blocked by CNQX. omega-Conotoxin (1 mu M) GVIA i nhibited EPSCs by 46%, while 30 nM and 1 mu M omega-agatoxin IVA produ ced 12% and 69% inhibition, respectively, consistent with coupling of N-, P- and Q-type Ca2+ channels to glutamatergic synaptic transmission . omega-GsTx SIA (1 mu M) rapidly, completely, and reversibly blocked glutamatergic EPSCs, but did not affect currents evoked by bath applic ation of kainate. Thus, omega-GsTx SIA blocks glutamatergic synaptic t ransmission 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 functi on following presynaptic block of synaptic transmission.