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

Abstract
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.
AuthorsWon Sun Park, Jin Han, Nari Kim, Jae-Hong Ko, Sung Joon Kim, Yung E Earm
JournalAmerican journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 289 Issue 6 Pg. H2461-7 (Dec 2005) ISSN: 0363-6135 [Print] United States
PMID16284107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Kir2.1 channel
  • Potassium Channels, Inwardly Rectifying
  • Sodium
Topics
  • Animals
  • Cell Hypoxia (physiology)
  • Cells, Cultured
  • Coronary Vessels (cytology, physiology)
  • Female
  • Ion Channel Gating (physiology)
  • Male
  • Muscle, Smooth, Vascular (physiology)
  • Myocytes, Smooth Muscle (physiology)
  • Potassium Channels, Inwardly Rectifying (physiology)
  • Rabbits
  • Sodium (metabolism)

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