ADENOSINE-ACTIVATED POTASSIUM CURRENT IN SMOOTH-MUSCLE CELLS ISOLATEDFROM THE PIG CORONARY-ARTERY

1. The perforated patch technique with nystatin or amphotericin was us ed to record whole cell currents activated by adenosine in smooth musc le cells isolated enzymatically from pig coronary arteries. 2. Adenosi ne (5-40 muM) activated an outward current at a holding potential of 0 mV in 5 mm [K+]o and an inward current at -60 mV in 143 mM [K+]o. The dependence of the reversal potential for the adenosine-activated curr ent on [K+]o suggests that it flows through K+ channels, while its cur rent-voltage relation is consistent with the channels showing little v oltage dependence. 3. The adenosine-activated current was inhibited by the sulphonylurea glibenclamide (5 muM) and by phencyclidine (5 muM). It was unaffected by charybdotoxin (50 nM) or apamin (100 nM), blocke rs of large and small conductance Ca2+-activated K+ channels respectiv ely. 4. At -60 mV in 143 mM K+ solution, openings of single channels p assing a current of just over -2 pA could sometimes be detected in the absence of adenosine. Openings became more frequent after the applica tion of adenosine, with several levels then being detected. Openings o f channels with a larger conductance were sometimes also seen in the p resence of adenosine. Fluctuation analysis gave somewhat lower estimat es of unitary current than did direct measurements. 5. The effect of a denosine could be mimicked by the A2 receptor agonist CCPA (2-chloro-N 6-cyclopentyladenosine), while the A2 agonist CGS 21680 2-carboxethyl) phenethylamino-5'-N-ethylearboxamido adenosine hydrochloride) was with out effect. The response to adenosine was inhibited by the A1 antagoni st DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by t he A2 antagonist CGS 15943A oro-2-(2-furanyl)-1,2,4-triazolo[1,5-C]qui nazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A, receptor to activate K+ channels. We consider it most l ikely that these are ATP-dependent K+ channels. We discuss the mechani sm by which K+ channel activation may lead to hyperpolarization and so vasorelaxation.