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 (<100 μm) coronary arteries of rabbit. Adenosine increased K IR currents in concentration-dependent manner (EC 50 = 9.4 ± 1.4 μM, 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 (10 μM), which was blocked by the addition of Ba 2+ (50 μM). 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.