Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels

Valerie A. Porter, Michael Rhodes, Helen L. Reeve, David N. Cornfield

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 ± 1.7% decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number6 25-6
StatePublished - Dec 31 2001

Fingerprint

Vasodilation
Oxygen
Calcium
Lung
Pulmonary Artery
Smooth Muscle Myocytes
Ryanodine
Potassium Channels
Calcium Signaling
Diltiazem
Caffeine
Fetal Blood
Vascular Smooth Muscle
Smooth Muscle
Sheep
Respiration
Air
Parturition

Keywords

  • Calcium-sensitive potassium channel
  • Smooth muscle cells
  • Spontaneous transient outward current

Cite this

Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels. / Porter, Valerie A.; Rhodes, Michael; Reeve, Helen L.; Cornfield, David N.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 6 25-6, 31.12.2001.

Research output: Contribution to journalArticle

@article{75d89642352043229864d147766e933c,
title = "Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels",
abstract = "O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 ± 1.7{\%} decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited {"}spontaneous transient outward currents,{"} indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.",
keywords = "Calcium-sensitive potassium channel, Smooth muscle cells, Spontaneous transient outward current",
author = "Porter, {Valerie A.} and Michael Rhodes and Reeve, {Helen L.} and Cornfield, {David N.}",
year = "2001",
month = "12",
day = "31",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology - Cell Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "6 25-6",

}

TY - JOUR

T1 - Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels

AU - Porter, Valerie A.

AU - Rhodes, Michael

AU - Reeve, Helen L.

AU - Cornfield, David N.

PY - 2001/12/31

Y1 - 2001/12/31

N2 - O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 ± 1.7% decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.

AB - O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 ± 1.7% decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.

KW - Calcium-sensitive potassium channel

KW - Smooth muscle cells

KW - Spontaneous transient outward current

UR - http://www.scopus.com/inward/record.url?scp=0035215756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035215756&partnerID=8YFLogxK

M3 - Article

C2 - 11704533

AN - SCOPUS:0035215756

VL - 281

JO - American Journal of Physiology - Cell Physiology

JF - American Journal of Physiology - Cell Physiology

SN - 0363-6143

IS - 6 25-6

ER -