Methoxyverapamil Reduction of Nicotine‐induced Catecholamine Release Involves Inhibition of Nicotinic Acetylcholine Receptor Currents

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Abstract
The mechanism by which the putative Ca2+ channel blocker methoxyverapamil (D600) inhibits nicotine‐induced catecholamine release was investigated in bovine adrenal chromaffin cells and in neurons from paravertebral sympathetic ganglia of chick embryos. We found D600 to prevent catecholamine release evoked by 30 s applications of nicotine with a significantly higher potency than the release induced either by 30 s K+ depolarizations or by electrical field stimulation of sympathetic neurons. Like the use‐dependent action of D600 upon Ca2+ channels, the magnitude of inhibition of the K+‐evoked secretion depended on the duration of stimulation (10 s to 5 min). Data on catecholamine release were supplemented by patch‐clamp recordings. We found whole‐cell currents in chromaffin cells evoked by (extrapolated) 0.5 s applications of nicotine to be significantly more sensitive to D600 than Ca2+ currents induced by a 0.5 s depolarization from ‐80 to 0 mV. In both instances, the potency of D600 depended on the duration of the (nicotinic and depolarizing) stimuli. Our data suggest that D600 inhibits nicotine‐induced catecholamine release by reducing nicotinic acetylcholine receptor currents rather than voltage‐gated Ca2+ currents. Hence, in chromaffin cells as well as in sympathetic neuronal preparations, D600 does not appear to be a suitable tool to investigate the part voltage‐activated Ca2+ currents play in cellular events induced by nicotine.