PMID- 11404263
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 281
IP  - 1
DP  - 2001 Jul
TI  - Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte 
      electrophysiological responses to hypoxia.
PG  - L202-8
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 Hif1a locus encoding HIF-1alpha [Hif1a(+/-)] and from their 
      wild-type [Hif1a(+/+)] 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 Hif1a(+/-) mice. Hypoxia 
      increased PASMC capacitance in Hif1a(+/+) mice but not in Hif1a(+/-) mice. 
      Chronic hypoxia depolarized and reduced K+ current density in PASMCs from 
      Hif1a(+/+) mice. In PASMCs from hypoxic Hif1a(+/-) mice, no reduction in K+ 
      current density was observed, and depolarization was significantly blunted. Thus 
      partial deficiency of HIF-1alpha is sufficient to impair hypoxia-induced 
      depolarization, reduction of K+ current density, and PASMC hypertrophy.
FAU - Shimoda, L A
AU  - Shimoda LA
AD  - Division of Pulmonary and Critical Care Medicine and Institute of Genetic 
      Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, 
      Maryland 21224, USA. shimodal@wech.jhu.edu
FAU - Manalo, D J
AU  - Manalo DJ
FAU - Sham, J S
AU  - Sham JS
FAU - Semenza, G L
AU  - Semenza GL
FAU - Sylvester, J T
AU  - Sylvester JT
LA  - eng
GR  - DK-39869/DK/NIDDK NIH HHS/United States
GR  - HL-51912/HL/NHLBI NIH HHS/United States
GR  - HL-55338/HL/NHLBI NIH HHS/United States
GR  - T32-HL-07534/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Potassium Channels)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - DNA-Binding Proteins/deficiency/genetics/*physiology
MH  - Electric Conductivity
MH  - Electrophysiology
MH  - Hematocrit
MH  - Hypertrophy, Right Ventricular/etiology
MH  - Hypoxia/blood/complications/*physiopathology
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Membrane Potentials
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout/genetics
MH  - Muscle, Smooth, Vascular/*physiology
MH  - Nuclear Proteins/deficiency/genetics/*physiology
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/physiology
MH  - Pulmonary Artery/pathology/*physiopathology
MH  - Reference Values
MH  - *Transcription Factors
EDAT- 2001/06/19 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
AID - 10.1152/ajplung.2001.281.1.L202 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L202-8. doi: 
      10.1152/ajplung.2001.281.1.L202.