Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats. |
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| Authors: | Kazuhiko Sonoyama Haruaki Ninomiya Osamu Igawa Yasuhiro Kaetsu Yoshiyuki Furuse Toshihiro Hamada Junichiro Miake Peili Li Yasutaka Yamamoto Kazuhide Ogino Akio Yoshida Shin-ichi Taniguchi Yasutaka Kurata Satoshi Matsuoka Toshio Narahashi Goshi Shiota Yoshihisa Nozawa Hiroaki Matsubara Masatsugu Horiuchi Yasuaki Shirayoshi Ichiro Hisatome |
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| Affiliation: | Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Yonago, Japan. |
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| 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. |
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