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

Won Sun Park, Jin Han, Nari Kim, Jae Hong Ko, Sungjoon Kim, Yung E. Earm

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Abstract

We examined the effects of acute hypoxia on Ba2+-sensitive inward rectifier K+ (KIR) current in rabbit coronary arterial smooth muscle cells. The amplitudes of KIR 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 KIR 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 KIR 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 GDPβS (1 mM) partially reduced (∼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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number6 58-6
DOIs
StatePublished - 1 Dec 2005

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Inwardly Rectifying Potassium Channel
Smooth Muscle Myocytes
Rabbits
KT 1
Hypoxia
Colforsin
GTP-Binding Proteins
Vasodilation
Western Blotting

Keywords

  • Coronary vasodilation
  • Inwardly rectifying K current
  • Kir2.1
  • Protein kinase A

Cite this

@article{222164a7abbd405eaec9b88bb76e1066,
title = "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+ (KIR) current in rabbit coronary arterial smooth muscle cells. The amplitudes of KIR 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 KIR 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 KIR 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 GDPβS (1 mM) partially reduced (∼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.",
keywords = "Coronary vasodilation, Inwardly rectifying K current, Kir2.1, Protein kinase A",
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Activation of inward rectifier K+ channels by hypoxia in rabbit coronary arterial smooth muscle cells. / Park, Won Sun; Han, Jin; Kim, Nari; Ko, Jae Hong; Kim, Sungjoon; Earm, Yung E.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 6 58-6, 01.12.2005.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activation of inward rectifier K+ channels by hypoxia in rabbit coronary arterial smooth muscle cells

AU - Park, Won Sun

AU - Han, Jin

AU - Kim, Nari

AU - Ko, Jae Hong

AU - Kim, Sungjoon

AU - Earm, Yung E.

PY - 2005/12/1

Y1 - 2005/12/1

N2 - We examined the effects of acute hypoxia on Ba2+-sensitive inward rectifier K+ (KIR) current in rabbit coronary arterial smooth muscle cells. The amplitudes of KIR 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 KIR 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 KIR 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 GDPβS (1 mM) partially reduced (∼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.

AB - We examined the effects of acute hypoxia on Ba2+-sensitive inward rectifier K+ (KIR) current in rabbit coronary arterial smooth muscle cells. The amplitudes of KIR 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 KIR 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 KIR 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 GDPβS (1 mM) partially reduced (∼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.

KW - Coronary vasodilation

KW - Inwardly rectifying K current

KW - Kir2.1

KW - Protein kinase A

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U2 - 10.1152/ajpheart.00331.2005

DO - 10.1152/ajpheart.00331.2005

M3 - Article

VL - 289

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 6 58-6

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