Activation of alpha 1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes.
The selective alpha 1-adrenergic agonist methoxamine (10(-4)-10(-3) M), in the presence of propranolol (10(-6) M), can reduce both the inwardly rectifying K+ background current (IK1) and the muscarinic cholinergic receptor-activated K+ current (IK,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+ currents(s) by alpha 1-adrenoceptor stimulation was insensitive to pre-treatment of atrial myocytes with pertussis toxin (0.15-0.5 micrograms/ml) and was irreversible following intracellular dialysis with the non-hydrolysable guanosine triphosphate (GTP) analogue, Gpp(NH)p (1-5 x 10(-3) M). Neither the protein kinase C (PKC) inhibitors, 1((5-isoquinolinesulphonyl)-2-methylpiperoxine (H-7) (5 x 10(-5) M) and staurosporine (1 x 10(-7) M), nor "downregulation" of PKC by prolonged phorbol ester exposure (5 x 10(-7) M, for 7-8 h) had an effect on the alpha 1-adrenergic modulation of this K+ current. Under cell-attached 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 alpha 1-adrenoceptor, 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.
Department of Medical Physiology and Medicine, University of Calgary, Alberta, Canada.
A P
AP
Braun
D
D
Fedida
W R
WR
Giles
D000200:Action Potentials / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D008729:Methoxamine / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D015221:Potassium Channels; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D008729:Methoxamine