Korean J Physiol Pharmacol.
1997 Oct;1(5):485-493.
alpha-Adrenergic and cholinergic receptor agonists modulate
voltage-gated Ca2+ channels
- Affiliations
-
- 1Department of Physiology, College of Veterinary Medicine.
- 2Department of Pharmacology, College of Medicine, Chonnam National University, Kwangju 500-757, South Korea.
- 3Department of Veterinary Medicine, Kangwon National University, Chuncheon, South Korea.
Abstract
-
We investigated the effect of alpha-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 (50 muM each) produced a rapid and
reversible reduction of the Ca2+ current by 17+/-6%, 19+/-3% and 18+/-4%,
respectively. Atropine, a muscarinic antagonist, blocked
carbachol-induced Ca2+ current inhibition to 3 +/- 1%. Norepinephrine
(50 muM) reduced Ca2+ current by 18 +/- 2%, while clonidine (50 muM), an
alpha2-adrenergic receptor agonist, inhibited Ca2+ current by only 4 +/-
1%. Yohimbine, an alpha2-adrenergic receptor antagonist, did not block
the inhibitory effect of norepinephrine on Ca2+ current, whereas
prazosin, an alpha1-adrenergic receptor antagonist, attenuated the
inhibitory effect of norepinephrine on Ca2+ current to 6 +/- 1%. This
pharmacology contrasts with alpha2-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 alpha1-adrenergic receptor. Pretreatment with pertussis
toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and
carbachol-induced Ca2+ current inhibition from 17 +/- 3% and 18 +/- 3% to
2 +/- 1% and 2 +/- 1%, respectively. These results demonstrate that
norepinephrine, through an alpha1-adrenergic receptor, and carbachol,
through a muscarinic receptor, inhibit Ca2+ currents in adult rat
trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding
proteins.