Abstract
The selective α1-adrenergic agonist methoxamine (10−4–10−3M), in the presence of propranolol (10−6M), can reduce both the inwardly rectifying K+ background current (I K1) and the muscarinic cholinergic receptor-activated K+ current (I K, ACh) in rabbit atrial myocytes resulting in action potential prolongation during the final phase of repolarization and a depolarization of the resting membrane potential. The reduction of these K+ current(s) by α1-adrenoceptor stimulation was insensitive to pre-treatment of artial myocytes with pertussis toxin (0.15–0.5 μg/ml) and was irreversible following intracellular dialysis with the non-hydrolysable guanosine triphosphate (GTP) analogue, Gpp(NH)p (1−5×10−3M). Neither the protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulphonyl)-2-methylpiperoxine (H-7) (5×10−5M) and staurosporine (1×10−7M), nor “downregulation” of PKC by prolonged phorbol ester exposure (5×10−7M, for 7–8 h) had an effect on the α1-adrenergic modulation of this K+ current. Under cellattached patch-clamp conditions, bath application of methoxamine reversibly decreased acetylcholine-induced single-channel activity, thus confirming the observed reduction of the ACh-induced current under whole-cell voltage clamp. These results demonstrate that the α1adrenoceptor, once activated, can reduce current through two different inwardly rectifying K+ channels in rabbit atrial myocytes. These current changes are mediated via a pertussis toxin-insensitive GTP-binding protein, and do not appear to involve the activation of PKC.
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Braun, A.P., Fedida, D. & Giles, W.R. Activation of α1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes. Pflügers Arch 421, 431–439 (1992). https://doi.org/10.1007/BF00370253
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DOI: https://doi.org/10.1007/BF00370253