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Activation of inward rectifier K⁺ channels by hypoxia in rabbit coronary arterial smooth muscle cells

¹Department of Physiology and National Research Laboratory for Cellular Signaling, Seoul National University College of Medicine, Seoul, Korea; and ²Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Biohealth Products Research Center, Cardiovascular and Metabolic Diseases Center, Inje University, Busan, Korea

Submitted 4 April 2005 ; accepted in final form 6 July 2005

We examined the effects of acute hypoxia on Ba²⁺-sensitive inward rectifier K⁺ (K_IR) current in rabbit coronary arterial smooth muscle cells. The amplitudes of K_IR current was definitely higher in the cells from small-diameter (<100 µm) coronary arterial smooth muscle cells (SCASMC, –12.8 ± 1.3 pA/pF at –140 mV) than those in large-diameter coronary arterial smooth muscle cells (>200 µm, LCASMC, –1.5 ± 0.1 pA pF^–1). Western blot analysis confirmed that Kir2.1 protein was expressed in SCASMC but not LCASMC. Hypoxia activated much more K_IR currents in symmetrical 140 K⁺. This effect was blocked by the adenylyl cyclase inhibitor SQ-22536 (10 µM) and mimicked by forskolin (10 µM) and dibutyryl-cAMP (500 µM). The production of cAMP in SCASMC increased 5.7-fold after 6 min of hypoxia. Hypoxia-induced increase in K_IR currents was abolished by the PKA inhibitors, Rp-8-(4-chlorophenylthio)-cAMPs (10 µM) and KT-5720 (1 µM). The inhibition of G protein with GDPS (1 mM) partially reduced (50%) the hypoxia-induced increase in K_IR currents. In Langendorff-perfused rabbit hearts, hypoxia increased coronary blood flow, an effect that was inhibited by Ba²⁺. In summary, hypoxia augments the K_IR currents in SCASMC via cAMP- and PKA-dependent signaling cascades, which might, at least partly, explain the hypoxia-induced coronary vasodilation.

inwardly rectifying K⁺ current; coronary vasodilation; protein kinase A; Kir2.1