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 microm) 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 microm, 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 KIR currents in symmetrical 140 K+. This effect was blocked by the
adenylyl cyclase inhibitor
SQ-22536 (10 microM) and mimicked by
forskolin (10 microM) and dibutyryl-cAMP (500 microM). The production of cAMP in SCASMC increased 5.7-fold after 6 min of
hypoxia.
Hypoxia-induced increase in KIR currents was abolished by the PKA inhibitors, Rp-8-(4-chlorophenylthio)-cAMPs (10 microM) and
KT-5720 (1 microM). The inhibition of
G protein with GDPbetaS (1 mM) partially reduced (approximately 50%) the
hypoxia-induced increase in KIR currents. In Langendorff-perfused rabbit hearts,
hypoxia increased coronary blood flow, an effect that was inhibited by Ba2+. In summary,
hypoxia augments the KIR currents in SCASMC via cAMP- and PKA-dependent signaling cascades, which might, at least partly, explain the
hypoxia-induced coronary vasodilation.