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• W2147330710 abstract "The effect of beta-adrenergic stimulation on endogenous G-protein-activated K(+) (GIRK) current has been investigated in atrial myocytes from hearts of adult rats. Beta-adrenergic stimulation (10 microm isoprenaline, Iso) had no effect on activation kinetics, peak current or steady-state current but resulted in slowing of deactivation upon washout of acetylcholine (ACh), the time constant (tau(d)) being increased by a factor of about 2.5. The effect of Iso could be mimicked by inclusion of cAMP (500 microm) in the filling solution of the patch clamp pipette. The Iso-induced increase in tau(d) was blocked by the selective beta(1) receptor antagonist CGP-20112A (2 microm) and by the PKA inhibitor H9 (100 microm included in the pipette solution). A candidate for mediating these effects is RGS10, one of the regulators of G-protein signalling (RGS) species expressed in cardiac myocytes. Overexpression of RGS10 by adenoviral gene transfer resulted in a reduction in tau(d) of 60%. Sensitivity of tau(d) to Iso remained in cells overexpressing RGS10. Overexpression of RGS4 caused a comparable reduction in tau(d), which became insensitive to Iso. Expression of an RGS10 carrying a mutation (RGS10-S168A), which deletes a PKA phosphorylation site, caused a decrease in tau(d) comparable to overexpression of wild-type RGS10. Sensitivity of tau(d) to Iso was lost in RGS10-S168A-expressing myocytes. Silencing of RGS10 by means of adenovirus-mediated transcription of a short hairpin RNA did not affect basal tau(d) but removed sensitivity to Iso. These data suggest that endogenous RGS10 has GTPase-activating protein (GAP) activity on the G-protein species that mediates activation of atrial GIRK channels. Moreover, RGS10, via PKA-dependent phosphorylation, enables a crosstalk between beta-adrenergic and muscarinic cholinergic signalling." @default.
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• W2147330710 date "2008-04-14" @default.
• W2147330710 modified "2023-10-17" @default.
• W2147330710 title "A role for RGS10 in β-adrenergic modulation of G-protein-activated K⁺(GIRK) channel current in rat atrial myocytes" @default.
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• W2147330710 doi "https://doi.org/10.1113/jphysiol.2007.148346" @default.
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