Protein kinase A-dependent activation of inward rectifier potassium channels by adenosine in rabbit coronary smooth muscle cells

We studied the effect of adenosine oil the Ba2+-sensitive K-IR channels in the smooth muscle cells isolated from the small-diameter (< 100 mu m) coronary arteries of rabbit. Adenosine increased K-IR currents in coneentration-dependent manner (EC50 = 9.4 +/- 1.4 mu M, 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-C1-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 (10 l.(M), which was blocked by the addition of Ba2+ (50 mu M). Above results suggest that adenosine increases Kip, Current via A(3) subtype through the activation of PKA in rabbit small-diameter coronary arterial smooth muscle cells. (c) 2005 Elsevier Inc. All rights reserved.