The polyamine spermine affects ω‐conotoxin binding and function at N‐type voltage‐sensitive calcium channels

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Abstract
1. The effects of the polyamines, spermine and spermidine on neuronal N-type voltage-sensitive calcium channels were investigated using the binding and function of the ligand .omega.-conotoxin GVIA (.omega.-CT). 2. Spermine and spermidine enhanced (EC50 approximately 0.16 and 0.45 .mu.M) and, at higher concentrations, inhibited (IC50 of 9 and 240 .mu.M) the binding of [125I].omega.-CT to rat hippocampal synaptosomes. 3. Spermine and, less potently, spermidine inhibited the neurotransmitter-mediated, .omega.-CT-sensitive, electrical-field-stimulated contractile responses of the rat vas deferens. 4. The polyamines also inhibited the phenylephrine-evoked contractile responses of the vas deferens with the same rank order, consistent with a postsynaptic mechanism of inhibition. 5. However, pre-exposure to spermine prevented the irreversible inhibition of vas deferens twitch responses by .omega.-CT (previously found to be presynaptic). The prevention of inhibition by .omega.-CT demonstrates that the neuronal binding of spermine and .omega.-CT is mutually exclusive. Thus spermine (and presumably spermidine at higher concentrations) appears to modulate the actions of .omega.-CT at N-type voltage-sensitive calcium channels.