Acute hypoxia activates store-operated ca2+ entry and increases intracellular ca2+ concentration in rat distal pulmonary venous smooth muscle cells

Gongyong Peng, Pixin Ran, Wenju Lu, Nanshan Zhong, Jian Wang

Research output: Contribution to journalArticle

Abstract

Rationale: Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side. Objectives: To investigate if acute hypoxia caused the increase of intracellular Ca2+ concentration ([Ca2+]i), and Ca2+ influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs). Methods: Fluorescent microscopy and fura-2 were used to measure effects of 4% O2 on [Ca2+]i and store-operated Ca2+ entry (SOCE) in isolated rat distal PVSMCs. Measurements and main results: In PVSMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca2+ entry through L-type voltage-depended Ca2+ channels (VDCC), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. Moreover, the increased [Ca2+]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85% was inhibited but [Ca2+]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca2+]i to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely abolished by perfusion with Ca2+-free KRBS. Conclusions: These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca2+]i in distal PVSMCs.

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalJournal of Thoracic Disease
Volume5
Issue number5
DOIs
StatePublished - Oct 2013

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Smooth Muscle Myocytes
Lung
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Nifedipine
Bicarbonates
Pulmonary Veins
Fura-2
Calcium Channel Blockers
Sarcoplasmic Reticulum
Calcium Channels
Vasoconstriction
Pulmonary Artery
Hypoxia
Microscopy
Perfusion
Salts
Fluorescence
Krebs-Ringer solution

Keywords

  • Calcium signaling
  • Intracellular Ca concentration ([Ca])
  • Pulmonary venous smooth muscle (PVSM)
  • Store-operated Ca entry (SOCE)

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Acute hypoxia activates store-operated ca2+ entry and increases intracellular ca2+ concentration in rat distal pulmonary venous smooth muscle cells. / Peng, Gongyong; Ran, Pixin; Lu, Wenju; Zhong, Nanshan; Wang, Jian.

In: Journal of Thoracic Disease, Vol. 5, No. 5, 10.2013, p. 605-612.

Research output: Contribution to journalArticle

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abstract = "Rationale: Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side. Objectives: To investigate if acute hypoxia caused the increase of intracellular Ca2+ concentration ([Ca2+]i), and Ca2+ influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs). Methods: Fluorescent microscopy and fura-2 were used to measure effects of 4{\%} O2 on [Ca2+]i and store-operated Ca2+ entry (SOCE) in isolated rat distal PVSMCs. Measurements and main results: In PVSMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca2+ entry through L-type voltage-depended Ca2+ channels (VDCC), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. Moreover, the increased [Ca2+]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85{\%} was inhibited but [Ca2+]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca2+]i to hypoxia by only 50{\%} at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely abolished by perfusion with Ca2+-free KRBS. Conclusions: These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca2+]i in distal PVSMCs.",
keywords = "Calcium signaling, Intracellular Ca concentration ([Ca]), Pulmonary venous smooth muscle (PVSM), Store-operated Ca entry (SOCE)",
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T1 - Acute hypoxia activates store-operated ca2+ entry and increases intracellular ca2+ concentration in rat distal pulmonary venous smooth muscle cells

AU - Peng, Gongyong

AU - Ran, Pixin

AU - Lu, Wenju

AU - Zhong, Nanshan

AU - Wang, Jian

PY - 2013/10

Y1 - 2013/10

N2 - Rationale: Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side. Objectives: To investigate if acute hypoxia caused the increase of intracellular Ca2+ concentration ([Ca2+]i), and Ca2+ influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs). Methods: Fluorescent microscopy and fura-2 were used to measure effects of 4% O2 on [Ca2+]i and store-operated Ca2+ entry (SOCE) in isolated rat distal PVSMCs. Measurements and main results: In PVSMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca2+ entry through L-type voltage-depended Ca2+ channels (VDCC), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. Moreover, the increased [Ca2+]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85% was inhibited but [Ca2+]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca2+]i to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely abolished by perfusion with Ca2+-free KRBS. Conclusions: These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca2+]i in distal PVSMCs.

AB - Rationale: Exposure to acute hypoxia causes vasoconstriction in both pulmonary arteries (PA) and pulmonary veins (PV). The mechanisms on the arterial side have been studied extensively. However, bare attention has been paid to the venous side. Objectives: To investigate if acute hypoxia caused the increase of intracellular Ca2+ concentration ([Ca2+]i), and Ca2+ influx through store-operated calcium channels (SOCC) in pulmonary venous smooth muscle cells (PVSMCs). Methods: Fluorescent microscopy and fura-2 were used to measure effects of 4% O2 on [Ca2+]i and store-operated Ca2+ entry (SOCE) in isolated rat distal PVSMCs. Measurements and main results: In PVSMCs perfused with Ca2+-free Krebs Ringer bicarbonate solution (KRBS) containing cyclopiazonic acid to deplete Ca2+ stores in the sarcoplasmic reticulum (SR) and nifedipine to prevent Ca2+ entry through L-type voltage-depended Ca2+ channels (VDCC), hypoxia markedly enhanced both the increase in [Ca2+]i caused by restoration of extracellular [Ca2+] and the rate at which extracellular Mn2+ quenched fura-2 fluorescence. Moreover, the increased [Ca2+]i in PVSMCs perfused with normal salt solution was completely blocked by SOCC antagonists SKF-96365 and NiCl2 at concentrations that SOCE >85% was inhibited but [Ca2+]i responses to 60 mM KCl were not altered. On the contrary, L-type VDCC antagonist nifedipine inhibited increase in [Ca2+]i to hypoxia by only 50% at concentrations that completely blocked responses to KCl. The increased [Ca2+]i caused by hypoxia was completely abolished by perfusion with Ca2+-free KRBS. Conclusions: These results suggest that acute hypoxia enhances SOCE via activating SOCCs, leading to increased [Ca2+]i in distal PVSMCs.

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KW - Intracellular Ca concentration ([Ca])

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KW - Store-operated Ca entry (SOCE)

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