title: Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.
abstract: We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.
authors.affiliation: Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sonoyama
authors.forename: Haruaki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Osamu
authors.initials: O
authors.lastname: Igawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kaetsu
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Furuse
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Junichiro
authors.initials: J
authors.lastname: Miake
authors.forename: Peili
authors.initials: P
authors.lastname: Li
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogino
authors.forename: Akio
authors.initials: A
authors.lastname: Yoshida
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kurata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Toshio
authors.initials: T
authors.lastname: Narahashi
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shirayoshi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression; D006325:Heart Atria / Q000166:cytology; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II