α-Adrenergic and Cholinergic Receptor Agonists Modulate Voltage- Gated Ca<SUP>2&#8290; </SUP>Channels

α-Adrenergic and Cholinergic Receptor Agonists Modulate Voltage- Gated Ca<SUP>2&#8290; </SUP>Channels

<P> We investigated the effect of α-adrenergic and cholinergic receptor agonists on Ca<SUP>2&#8290; </SUP>current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 &#12557;M each) produced a rapid and reversible reduction of the Ca<SUP>2&#8290;</SUP> current by 17&#8273;6%, 19&#8273;3%, and 18&#8273;4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced Ca<SUP>2&#8290;</SUP> current inhibition to 3&#8273;1%. Norepinephrine (50 &#12557;M) reduced Ca<SUP>2&#8290;</SUP> current by 18&#8273;2%, while clonidine (50 &#12557;M), an α<SUB>2</SUB>-adrenergic receptor agonist, inhibited Ca<SUP>2&#8290;</SUP> current by only 4&#8273;1%. Yohimbine, an α<SUB>2</SUB>-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca<SUP>2&#8290;</SUP> current, whereas prazosin, an α<SUB>1</SUB>-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca<SUP>2&#8290; </SUP>current to 6&#8273;1%. This pharmacology contrasts with α<SUB>2</SUB>-adrenergic receptor modulation of Ca<SUP>2&#8290; </SUP>channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca<SUP>2&#8290; </SUP>channel by norepinephrine is mediated via an α<SUB>1</SUB>-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca<SUP>2&#8290; </SUP>current inhibition from 17&#8273;3% and 18&#8273;3% to 2&#8273;1% and 2&#8273;1%, respectively. These results demonstrate that norepinephrine, through an α<SUB>1</SUB>-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca<SUP>2&#8290; </SUP>currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.