Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.
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.
Sonoyama
Kazuhiko
K
Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
Ninomiya
Haruaki
H
Igawa
Osamu
O
Kaetsu
Yasuhiro
Y
Furuse
Yoshiyuki
Y
Hamada
Toshihiro
T
Miake
Junichiro
J
Li
Peili
P
Yamamoto
Yasutaka
Y
Ogino
Kazuhide
K
Yoshida
Akio
A
Taniguchi
Shin-ichi
S
Kurata
Yasutaka
Y
Matsuoka
Satoshi
S
Narahashi
Toshio
T
Shiota
Goshi
G
Nozawa
Yoshihisa
Y
Matsubara
Hiroaki
H
Horiuchi
Masatsugu
M
Shirayoshi
Yasuaki
Y
Hisatome
Ichiro
I
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
D024661:Potassium Channels, Inwardly Rectifying; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II