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 AT1 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 Giα-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 IK1 in cells from spontaneously hypertensive rats (SHR). AT1 immunoprecipitation from atrial extracts revealed decreased amounts of Giα-2 and Giα-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT1 with Giα proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.
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Sonoyama, K., Ninomiya, H., Igawa, O. et al. Inhibition of Inward Rectifier K+ Currents by Angiotensin II in Rat Atrial Myocytes: Lack of Effects in Cells from Spontaneously Hypertensive Rats. Hypertens Res 29, 923–934 (2006). https://doi.org/10.1291/hypres.29.923
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DOI: https://doi.org/10.1291/hypres.29.923