Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

Larissa Shimoda, Dominador J. Manalo, James Sham, Gregg L Semenza, J. T. Sylvester

Research output: Contribution to journalArticle

Abstract

Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1α locus encoding HIF-1α [Hif1α(+/-)] and from their wild-type [Hif1α(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1α(+/-) mice. Hypoxia increased PASMC capacitance in Hif1α(+/+) mice but not in Hif1α(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1α(+/+) mice. In PASMCs from hypoxic Hif1α(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1α is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number1 25-1
StatePublished - 2001

Fingerprint

Hypoxia-Inducible Factor 1
Muscle Cells
Smooth Muscle Myocytes
Lung
Right Ventricular Hypertrophy
Polycythemia
Hematocrit
Pulmonary Hypertension
Membrane Potentials
Hypertrophy
Heart Ventricles
Hypoxia
Arteries
Alleles
Air
Weights and Measures

Keywords

  • Hypoxia-inducible factor-1
  • Membrane potential
  • Pulmonary arterial smooth muscle cell
  • Pulmonary hypertension
  • Voltage-gated potassium current

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

@article{39320bf4849347e4a1614d6732b40a7d,
title = "Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia",
abstract = "Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1α locus encoding HIF-1α [Hif1α(+/-)] and from their wild-type [Hif1α(+/+)] littermates after 3 wk in air or 10{\%} O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1α(+/-) mice. Hypoxia increased PASMC capacitance in Hif1α(+/+) mice but not in Hif1α(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1α(+/+) mice. In PASMCs from hypoxic Hif1α(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1α is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.",
keywords = "Hypoxia-inducible factor-1, Membrane potential, Pulmonary arterial smooth muscle cell, Pulmonary hypertension, Voltage-gated potassium current",
author = "Larissa Shimoda and Manalo, {Dominador J.} and James Sham and Semenza, {Gregg L} and Sylvester, {J. T.}",
year = "2001",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 25-1",

}

TY - JOUR

T1 - Partial HIF-1α deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia

AU - Shimoda, Larissa

AU - Manalo, Dominador J.

AU - Sham, James

AU - Semenza, Gregg L

AU - Sylvester, J. T.

PY - 2001

Y1 - 2001

N2 - Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1α locus encoding HIF-1α [Hif1α(+/-)] and from their wild-type [Hif1α(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1α(+/-) mice. Hypoxia increased PASMC capacitance in Hif1α(+/+) mice but not in Hif1α(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1α(+/+) mice. In PASMCs from hypoxic Hif1α(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1α is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.

AB - Chronic hypoxia depolarizes and reduces K+ current in pulmonary arterial smooth muscle cells (PASMCs). Our laboratory previously demonstrated that hypoxia-inducible factor-1 (HIF-1) contributed to the development of hypoxic pulmonary hypertension. In this study, electrophysiological parameters were measured in PASMCs isolated from intrapulmonary arteries of mice with one null allele at the Hif1α locus encoding HIF-1α [Hif1α(+/-)] and from their wild-type [Hif1α(+/+)] littermates after 3 wk in air or 10% O2. Hematocrit and right ventricular wall and left ventricle plus septum weights were measured. Capacitance, K+ current, and membrane potential were measured with whole cell patch clamp. Similar to our laboratory's previous results, hypoxia-induced right ventricular hypertrophy and polycythemia were blunted in Hif1α(+/-) mice. Hypoxia increased PASMC capacitance in Hif1α(+/+) mice but not in Hif1α(+/-) mice. Chronic hypoxia depolarized and reduced K+ current density in PASMCs from Hif1α(+/+) mice. In PASMCs from hypoxic Hif1α(+/-) mice, no reduction in K+ current density was observed, and depolarization was significantly blunted. Thus partial deficiency of HIF-1α is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy.

KW - Hypoxia-inducible factor-1

KW - Membrane potential

KW - Pulmonary arterial smooth muscle cell

KW - Pulmonary hypertension

KW - Voltage-gated potassium current

UR - http://www.scopus.com/inward/record.url?scp=0034815688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034815688&partnerID=8YFLogxK

M3 - Article

VL - 281

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 1 25-1

ER -