ω-Grammotoxin SIA blocks multiple, voltage-gated, Ca2+ channel subtypes in cultured rat hippocampal neurons

Timothy M. Piser, Richard A. Lampe, Richard A. Keith, Stanley A Thayer

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

ω-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 ω- grammotoxin SIA, whole-cell Ba2+ current (I(Ba)) was measured in cultured rat hippocampal neurons. Selective Ca2+ channel blockers were used to identify components of I(Ba) mediated by Ca2+ channel subtypes. ω-Agatoxin IVA at 30 nM, 1 μM ω-conotoxin GVIA, and 3 μM ω-conotoxin MVIIC, applied consecutively, each elicited a fractional increase in the cumulative block of I(Ba), identifying components of I(Ba) mediated by P-, N-, and Q-type calcium channels. ω-Grammotoxin at 1 μM, a maximally effective concentration, blocked 52% of I(Ba). ω-Conotoxin MVIIC and the combination of ω-conotoxin GVIA and micromolar ω-agatoxin IVA blocked 52% and 54% of I(Ba), respectively, and block of I(Ba) by ω-grammotoxin SIA was mutually occlusive of block of I(Ba) by either treatment, both of which block N-, P-, and Q- type Ca2+ channels. The L channel blocker nimodipine produced identical block of I(Ba) in the presence and absence of ω-grammotoxin SIA. These results indicate that ω-grammotoxin SIA blocks N-, P-, and Q-type but not L- type voltage-gated calcium channels. Block of I(Ba) by ω-grammotoxin SIA was faster in onset and less sensitive to external divalent cation concentrations than was block by ω-conotoxin MVIIC, and it was rapidly and substantially reversible. Rapid onset, relative insensitivity to divalent cation concentrations, and reversibility render ω-grammotoxin SIA a useful tool for inhibition of neuronal voltage-gated Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalMolecular Pharmacology
Volume48
Issue number1
StatePublished - 1995

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