title: Protein kinase A-dependent activation of inward rectifier potassium channels by adenosine in rabbit coronary smooth muscle cells.
abstract: We studied the effect of adenosine on the Ba(2+)-sensitive K(IR) channels in the smooth muscle cells isolated from the small-diameter (<100microm) coronary arteries of rabbit. Adenosine increased K(IR) currents in concentration-dependent manner (EC(50)=9.4+/-1.4microM, maximum increase of 153%). The adenosine-induced stimulation of K(IR) current was blocked by adenylyl cyclase inhibitor, SQ22536 and was mimicked by adenylyl cyclase activator, forskolin. The adenosine-induced increase of current was blocked by cyclic AMP-dependent protein kinase (PKA) inhibitors, KT 5720 and Rp-8-CPT-cAMPs. The adenosine-induced increase of K(IR) currents was blocked by an A(3)-selective antagonist MRS1334, while the antagonists of other subtypes (DPCPX for A(1), ZM241385 for A(2A), and alloxazine for A(2B)) were all ineffective. Furthermore, an A(3)-selective agonist, 2-Cl-IB-MECA induced increase of K(IR) currents. We also examined the effect of adenosine on coronary blood flow (CBF) rate by using the Langendorff-perfused heart. In the presence of glibenclamide to exclude the effects of ATP-sensitive K(+) (K(ATP)) channels, CBF was increased by adenosine (10microM), which was blocked by the addition of Ba(2+) (50microM). Above results suggest that adenosine increases K(IR) current via A(3) subtype through the activation of PKA in rabbit small-diameter coronary arterial smooth muscle cells.
authors.affiliation: Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000737:chemistry / Q000494:pharmacology; D002413:Cations, Divalent; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011817:Rabbits; D043684:Receptor, Adenosine A3 / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D024661:Potassium Channels, Inwardly Rectifying; D043684:Receptor, Adenosine A3; D001464:Barium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000241:Adenosine