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 (I-K1) in rat atrial myocytes. [I-125]Ang II-binding assays revealed the presence of both Ang II type 1 (AT(1)) and type 2 (AT(2)) receptors in atrial membrane preparations. Ang II inhibited I-K1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT(1) antagonist RNH6270 but not at all by the AT(2) antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of G(i alpha-3) abolished the inhibition by Ang II, indicating the role of a G(i)-dependent signaling pathway. Accordingly, Ang II failed to inhibit I-K1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [I-125]Ang II, Ang II failed to affect I-K1 in cells from spontaneously hypertensive rats (SHR). AT(1) immunoprecipitation from atrial extracts revealed decreased amounts of G(i alpha-2) and G(i alpha-3) proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT(1) with G(i alpha) proteins may underlie the unresponsiveness of atrial I-K1 to Ang II in SHR cells.