Activation of inward rectifier K+ channels by hypoxia in rabbit coronary arterial smooth muscle cells.
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.
Park
Won Sun
WS
Dept. of Physiology and National Research Lab. for Cellular Signaling, Seoul National Univ. Coll. of Medicine, 28 Yonkeun-Dong, Chongno-Gu, Seoul 110-799 Korea.
Han
Jin
J
Kim
Nari
N
Ko
Jae-Hong
JH
Kim
Sung Joon
SJ
Earm
Yung E
YE
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D012964:Sodium