Omega-grammotoxin SIA blocks multiple, voltage-gated, Ca2+ channel subtypes in cultured rat hippocampal neurons.
Omega-Grammotoxin SIA is a peptide isolated from tarantula venom on the basis of its ability to block the voltage-gated Ca2+ channels that mediate glutamate release. To determine the Ca2+ channel subtype selectivity of omega-grammotoxin SIA, whole-cell Ba2+ current (IBa) was measured in cultured rat hippocampal neurons. Selective Ca2+ channel blockers were used to identify components of IBa mediated by Ca2+ channel subtypes. omega-Agatoxin IVA at 30 nM, 1 microM omega-conotoxin GVIA, and 3 microM omega-contoxin MVIIC, applied consecutively, each elicited a fractional increase in the cumulative block of IBa, identifying components of IBa mediated by P-, N-, and Q-type calcium channels. omega-Grammotoxin at 1 microM, a maximally effective concentration, blocked 52% of IBa. omega-Conotoxin MVIIC and the combination of omega-conotoxin GVIA and micromolar omega-agatoxin IVA blocked 52% and 54% of IBa, respectively, and block of IBa by omega-grammotoxin SIA was mutually occlusive of block of IBa by either treatment, both of which block N-, P-, and Q-type Ca2+ channels. The L channel blocker nimodipine produced identical block of IBa in the presence and absence of omega-grammotoxin SIA. These results indicate that omega-grammotoxin SIA blocks N-, P-, and Q-type but not L-type voltage-gated calcium channels. Block of IBa by omega-grammotoxin SIA was faster in onset and less sensitive to external divalent cation concentrations than was block by omega-conotoxin MVIIC, and it was rapidly and substantially reversible. Rapid onset, relative insensitivity to divalent cation concentrations, and reversibility render omega-grammotoxin SIA a useful tool for inhibition of neuronal voltage-gated Ca2+ channels.
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*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010456:Peptides, Cyclic; D013111:Spider Venoms; C082807:omega-grammotoxin SIA