Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium channels in vascular smooth muscle of the canine saphenous vein.
Experiments were designed to determine how isoproterenol affects the cell membrane potential of smooth muscle cells of the canine saphenous vein. Measurements of membrane potential were performed using glass microelectrodes. Isoproterenol (10(-9) to 10(-6) M) caused sustained, concentration-dependent membrane hyperpolarizations in tissues with and without endothelium. ICI 118,551 (a selective beta 2-adrenoceptor antagonist), but not atenolol (a selective beta 1-adrenoceptor antagonist), abolished the hyperpolarization to isoproterenol. Forskolin, an activator of adenylate cyclase, produced sustained hyperpolarizations, which were not mimicked by 1,9-dideoxyforskolin. Incubation with either ouabain or extracellular K(+)-free solution did not inhibit the electrical response to isoproterenol. Glibenclamide (a selective ATP-sensitive K+ channel antagonist) attenuated the hyperpolarizations induced by either isoproterenol or forskolin, whereas charybdotoxin (an inhibitor of large conductance Ca(++)-activated K+ channels) did not. These findings suggest that isoproterenol opens ATP-sensitive K+ channels indirectly through activation of adenylate cyclase in the smooth muscle of the canine saphenous vein. The adrenergic receptor involved belongs to the beta 2-adrenoceptor subtype.
Nakashima
M
M
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
Vanhoutte
P M
PM
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D018999:Charybdotoxin; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012501:Saphenous Vein; D012604:Scorpion Venoms / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D015221:Potassium Channels; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D012604:Scorpion Venoms; D018999:Charybdotoxin; D005576:Colforsin; D015016:Yohimbine; C026777:ICI 118551; D001262:Atenolol; D010042:Ouabain; D007545:Isoproterenol; D005905:Glyburide