A role for RGS10 in beta-adrenergic modulation of G-protein-activated K+ (GIRK) channel current in rat atrial myocytes

J Physiol. 2008 Apr 15;586(8):2049-60. doi: 10.1113/jphysiol.2007.148346. Epub 2008 Feb 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Function / physiology*
  • Cells, Cultured
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • Heart Atria / cytology
  • Ion Channel Gating / physiology*
  • Male
  • Membrane Potentials / physiology*
  • Myocytes, Cardiac / physiology*
  • Potassium / metabolism*
  • RGS Proteins / metabolism*
  • Rats
  • Rats, Inbred WKY


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • RGS Proteins
  • Rgs10 protein, mouse
  • Potassium