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

被引:21
作者
Sorota, S [1 ]
Rybina, I [1 ]
Yamamoto, A [1 ]
Du, XY [1 ]
机构
[1] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1999年 / 514卷 / 02期
关键词
D O I
10.1111/j.1469-7793.1999.413ae.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. G protein beta gamma subunits activate the acetylcholine-induced potassium current I-K,I-Ach. There is no evidence of specificity at the level of the beta gamma subunits. Therefore all G protein-coupled receptors in atrial myocytes should be able to activate I-K,I-ACh. Paradoxically, it is often stated that isoprenaline does not activate I-K,I-ACh. Rationales to explain this negative result include insufficient concentrations of G(s) in the atrium or restricted access of G(s)-derived beta gamma subunits to the I-K,I-ACh channel. We took advantage of a non-specific increase in G(s) that results after infection with adenovirus. 2. Adenoviral infection unmasked a 1 mu M isoprenaline-induced I-K,I-ACh which was prevented by propranolol. Isoprenaline occasionally activated I-K,I-ACh 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,I-ACh. Forskolin (10 mu M) did not activate I-K,I-ACh. Inhibition of adenylyl cyclase with cytoplasmic application of 300 mu M 2'-deoxyadenosine 3'-monophosphate did not prevent the activation of I-K,I-ACh by isoprenaline. 5. Cytoplasmic application of a beta gamma binding peptide derived from the C terminus of beta-adrenergic receptor kinase 1 (50 mu M) prevented the effect of isoprenaline on I-K,I-ACh. The peptide did not prevent the stimulation of the L-type calcium current by isoprenaline. 6. The results indicate that beta-adrenoceptors can activate I-K,I-ACh in atrial myocytes through the release of beta gamma subunits from G(s).
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页码:413 / 423
页数:11
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