Isoprenaline can activate the acetylcholine‐induced K + current in canine atrial myocytes via G s ‐derived βγ subunits

1 G protein βγ subunits activate the acetylcholine‐induced potassium current I k,ac h . There is no evidence of specificity at the level of the βγ subunits. Therefore all G protein‐coupled receptors in atrial myocytes should be able to activate I k,ac h . Paradoxically, it is often stated that isoprenaline does not activate I k,ac h . Rationales to explain this negative result include insufficient concentrations of G s in the atrium or restricted access of G s ‐derived βγ subunits to the I k,ac h channel. We took advantage of a non‐specific increase in G s that results after infection with adenovirus. 2 Adenoviral infection unmasked a 1 μ m isoprenaline‐induced I k,ac h which was prevented by propranolol. Isoprenaline occasionally activated I k,ac h in uninfected and freshly dissociated atrial myocytes but the effect was larger and more consistent in infected myocytes. 3 Pertussis toxin pretreatment (100 ng ml −1 overnight) did not block the effect of isoprenaline. The effect of isoprenaline became persistent if cells were pretreated with cholera toxin (200 ng nl −1 ). 4 Signal transduction events distal to adenylyl cyclase were not involved in isoprenaline‐induced I k,ac h . Forskolin (10 μ m ) did not activate I k,ac h . Inhibition of adenylyl cyclase with cytoplasmic application of 300 μ m 2′‐deoxyadenosine 3′‐monophosphate did not prevent the activation of I k,ac h by isoprenaline. 5 Cytoplasmic application of a βγ binding peptide derived from the C terminus of β‐adrenergic receptor kinase 1 (50 μ m ) prevented the effect of isoprenaline on I k,ac h . The peptide did not prevent the stimulation of the L‐type calcium current by isoprenaline. 6 The results indicate that β‐adrenoceptors can activate I k,ac h in atrial myocytes through the release of βγ subunits from G s .