Abstract

The peptide toxin ω-Aga-IVA blocked P-type Ca 2+ channel current in rat Purkinje neurons (K D ≈ 2 nM) but had no effect on identified T-type, L-type, or N-type currents in a variety of central and peripheral neurons. ω-Aga-IVA blocked a substantial fraction of high threshold Ca 2+ channel current in neurons from the hippocampal CA1 region (mean 26%), visual cortex (32%), spinal cord (45%), and dorsal root ganglia (23%), but less in hippocampal CA3 neurons (14%) and none in sympathetic neurons. In all cases, ω-Aga-IVA block could be reversed by a brief train of strong depolarizations. There was no overlap between current blocked by ω-Aga-IVA and the fractions blocked by dihydropyridines and ω-conotoxin GVIA, but not all current resistant to dihydropyridines and ω-conotoxin was blocked by ω-Aga-IVA. The results suggest that ω-Aga-IVA is highly selective for P-type channels and that many central neurons and some peripheral neurons possess substantial P-type current.

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