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We investigated the effect of α?adrenergic and cholinergic receptor agonists on Ca2+ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50μMeach) produced a rapid and reversible reduction of the Ca2+ current by 17±6, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced Ca2+ current inhibition to 3±1. Norepinephrine (50μM) reduced Ca2+ current by 18±2, while clonidine (50μM), an α2?adrenergic receptor agonist, inhibited Ca2+ current by only 4±1. Yohimbine, an α2?adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca2+ current, whereas prazosin, an α1?adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca2+ current to 6±1. This pharmacology contrasts with α2?adrenergic receptor modulation of Ca2+ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca2+ channel by norepinephrine is mediated via an α1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca2+ current inhibition from 17±3, respectively. These results demonstrate that norepinephrine, through an α1?adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca2+ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.
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