title: Adrenergic and cholinergic inhibition of Ca2+ channels mediated by different GTP-binding proteins in rat sympathetic neurones.
abstract: Effects of acetylcholine (ACh) and noradrenaline (NA) on voltage-gated ion channels of sympathetic neurones acutely dissociated from rat superior cervical ganglion (SCG) were examined using the whole-cell voltage-clamp technique. Depolarizing voltage steps elicited two types of low- and high-voltage-activated (LVA and HVA) Ca2+ currents. Pressure applications of ACh and NA produced concentration-dependent inhibition of the HVA Ca2+ current without affecting the LVA Ca2+ current. The inhibitory action of ACh on the Ca2+ current was blocked by a muscarinic antagonist, atropine. The action of NA was suppressed by an alpha 2-adrenergic antagonist, yohimbine, but not by an alpha 1-adrenergic antagonist, prazosin. Delayed rectifying outward K+ currents and inward rectifying K+ current were not affected by either ACh or NA. Tetrodotoxin-sensitive and -insensitive Na+ currents also remained unaffected under actions of ACh and NA. When recorded with electrode containing guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), the inhibitory actions of ACh and NA on Ca2+ currents became irreversible. After treatment of SCG neurones with pertussis toxin, the inhibitory action of ACh on the Ca2+ current was almost completely abolished, whereas the action of NA was only partially reduced. The results suggest that ACh and NA differentially inhibit the HVA Ca2+ current via different G proteins coupling muscarinic and alpha 2-adrenergic receptors to Ca2+ channels in rat SCG neurones.
authors.affiliation: Laboratory of Cellular Physiology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
authors.forename: S Y
authors.initials: SY
authors.lastname: Song
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: S
authors.initials: S
authors.lastname: Konishi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine