title: Alpha 1-adrenoceptor-activated cation currents in neurones acutely isolated from rat cardiac parasympathetic ganglia.
abstract: The noradrenaline (NA)-induced cation current was investigated in neurones freshly isolated from rat cardiac parasympathetic ganglia using the nystatin-perforated patch recording configuration. Under current-clamp conditions, NA depolarized the membrane, eliciting repetitive action potentials. NA evoked an inward cation current under voltage-clamp conditions at a holding potential of -60 mV. The NA-induced current was inhibited by extracellular Ca2+ or Mg2+, with a half-maximal concentration of 13 microM for Ca2+ and 1.2 mM for Mg2+. Cirazoline mimicked the NA response, and prazosin and WB-4101 inhibited the NA-induced current, suggesting the contribution of an alpha1-adrenoceptor. The NA-induced current was inhibited by U73122, a phospholipase C (PLC) inhibitor. The membrane-permeable IP3 receptor blocker xestospongin-C also blocked the NA-induced current. Furthermore, pretreatment with thapsigargin and BAPTA-AM could inhibit the NA response while KN-62, phorbol 12-myristate 13-acetate (PMA) and staurosporine had no effect. These results suggest that NA activates the extracellular Ca2+- and Mg2+-sensitive cation channels via alpha 1-adrenoceptors in neurones freshly isolated from rat cardiac parasympathetic ganglia. This activation mechanism also involves phosphoinositide breakdown, release of Ca2+ from intracellular Ca2+ stores and calmodulin. The cation channels activated by NA may play an important role in neuronal membrane depolarization in rat cardiac ganglia.
authors.affiliation: Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. h-ishi@physiol2.med.kyushu-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Mari
authors.initials: M
authors.lastname: Umezu
authors.forename: Il-Sung
authors.initials: IS
authors.lastname: Jang
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ito
authors.forename: Norio
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D004594:Electrophysiology; D005470:Fluorometry; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D007476:Ionophores; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D009761:Nystatin; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D002147:Calmodulin; D007473:Ion Channels; D007476:Ionophores; D018340:Receptors, Adrenergic, alpha-1; D009761:Nystatin; D010738:Type C Phospholipases; D002118:Calcium; D009638:Norepinephrine