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Isoprenaline can activate the acetylcholine-induced K⁺ current in canine atrial myocytes via G_s-derived subunits

Steve Sorota, Irina Rybina, Ai Yamamoto and Xiao-Yi Du

G protein subunits activate the acetylcholine-induced potassium current I_K,ACh. There is no evidence of specificity at the level of the subunits. Therefore all G protein-coupled receptors in atrial myocytes should be able to activate I_K,ACh. Paradoxically, it is often stated that isoprenaline does not activate I_K,ACh. Rationales to explain this negative result include insufficient concentrations of G_s in the atrium or restricted access of G_s-derived subunits to the I_K,ACh channel. We took advantage of a non-specific increase in G_s that results after infection with adenovirus.

Adenoviral infection unmasked a 1 µM isoprenaline-induced I_K,ACh which was prevented by propranolol. Isoprenaline occasionally activated I_K,ACh in uninfected and freshly dissociated atrial myocytes but the effect was larger and more consistent in infected myocytes.

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).

Signal transduction events distal to adenylyl cyclase were not involved in isoprenaline-induced I_K,ACh. Forskolin (10 µM) did not activate I_K,ACh. Inhibition of adenylyl cyclase with cytoplasmic application of 300 µM 2'-deoxyadenosine 3'-monophosphate did not prevent the activation of I_K,ACh by isoprenaline.

Cytoplasmic application of a binding peptide derived from the C terminus of -adrenergic receptor kinase 1 (50 µM) prevented the effect of isoprenaline on I_K,ACh. The peptide did not prevent the stimulation of the L-type calcium current by isoprenaline.

The results indicate that -adrenoceptors can activate I_K,ACh in atrial myocytes through the release of subunits from G_s.

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