Heterogeneity of hypoxia-mediated decrease in IK(V) and increase in [Ca2+]cyt in pulmonary artery smooth muscle cells

Oleksandr Platoshyn, Ying Yu, Eun A. Ko, Carmelle V. Remillard, Jason Yuan

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hypoxic pulmonary vasoconstriction is caused by a rise in cytosolic Ca 2+ ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) via multiple mechanisms. PASMC consist of heterogeneous phenotypes defined by contractility, proliferation, and apoptosis as well as by differences in expression and function of various genes. In rat PASMC, hypoxia-mediated decrease in voltage-gated K+ (Kv) currents (I K(V)) and increase in [Ca2+]cyt were not uniformly distributed in all PASMC tested. Acute hypoxia decreased I K(V) and increased [Ca2+]cyt in ∼46% and ∼53% of PASMC, respectively. Using combined techniques of single-cell RTPCR and patch clamp, we show here that mRNA expression level of Kv1.5 in hypoxia-sensitive PASMC (in which hypoxia reduced IK(V)) was much greater than in hypoxia-insensitive cells (in which hypoxia negligibly affected IK(V)). These results demonstrate that 1) different PASMC express different Kv channel α- and β-subunits, and 2) the sensitivity of a PASMC to acute hypoxia partially depends on the expression level of Kv1.5 channels; hypoxia reduces whole-cell IK(V) only in PASMC that express high level of Kv1.5. In addition, the acute hypoxia-mediated changes in [Ca2+]cyt also vary in different PASMC. Hypoxia increases [Ca2+]cyt only in 34% of cells tested, and the different sensitivity of [Ca2+]cyt to hypoxia was not related to the resting [Ca2+]cyt. An intrinsic mechanism within each individual cell may be involved in the heterogeneity of hypoxia-mediated effect on [Ca2+]cyt in PASMC. These data suggest that the heterogeneity of PASMC may partially be related to different expression levels and functional sensitivity of Kv channels to hypoxia and to differences in intrinsic mechanisms involved in regulating [Ca2+]cyt.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

Pulmonary Artery
Smooth Muscle Myocytes
Hypoxia
Cell Hypoxia
Vasoconstriction
Apoptosis
Phenotype
Lung
Messenger RNA

Keywords

  • Kv1.5
  • Membrane potential
  • Vascular smooth muscle cells
  • Voltage-gated K channel

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Heterogeneity of hypoxia-mediated decrease in IK(V) and increase in [Ca2+]cyt in pulmonary artery smooth muscle cells. / Platoshyn, Oleksandr; Yu, Ying; Ko, Eun A.; Remillard, Carmelle V.; Yuan, Jason.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 293, No. 2, 08.2007.

Research output: Contribution to journalArticle

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abstract = "Hypoxic pulmonary vasoconstriction is caused by a rise in cytosolic Ca 2+ ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMC) via multiple mechanisms. PASMC consist of heterogeneous phenotypes defined by contractility, proliferation, and apoptosis as well as by differences in expression and function of various genes. In rat PASMC, hypoxia-mediated decrease in voltage-gated K+ (Kv) currents (I K(V)) and increase in [Ca2+]cyt were not uniformly distributed in all PASMC tested. Acute hypoxia decreased I K(V) and increased [Ca2+]cyt in ∼46{\%} and ∼53{\%} of PASMC, respectively. Using combined techniques of single-cell RTPCR and patch clamp, we show here that mRNA expression level of Kv1.5 in hypoxia-sensitive PASMC (in which hypoxia reduced IK(V)) was much greater than in hypoxia-insensitive cells (in which hypoxia negligibly affected IK(V)). These results demonstrate that 1) different PASMC express different Kv channel α- and β-subunits, and 2) the sensitivity of a PASMC to acute hypoxia partially depends on the expression level of Kv1.5 channels; hypoxia reduces whole-cell IK(V) only in PASMC that express high level of Kv1.5. In addition, the acute hypoxia-mediated changes in [Ca2+]cyt also vary in different PASMC. Hypoxia increases [Ca2+]cyt only in 34{\%} of cells tested, and the different sensitivity of [Ca2+]cyt to hypoxia was not related to the resting [Ca2+]cyt. An intrinsic mechanism within each individual cell may be involved in the heterogeneity of hypoxia-mediated effect on [Ca2+]cyt in PASMC. These data suggest that the heterogeneity of PASMC may partially be related to different expression levels and functional sensitivity of Kv channels to hypoxia and to differences in intrinsic mechanisms involved in regulating [Ca2+]cyt.",
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