Journal article
Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage‐gated potassium channel Kv1.5
The FASEB journal, Vol.15(10), pp.1801-1803
08/2001
DOI: 10.1096/fj.00-0649fje
PMID: 11481235
Abstract
ABSTRACT
Hypoxic pulmonary vasoconstriction (HPV) is initiated by the inhibition of several 4‐aminopyridine (4‐AP)‐sensitive, voltage‐gated, K+ channels (Kv). Several O2‐sensitive candidate channels (Kv1.2, Kv1.5, Kv2.1, and Kv3.1b) have been proposed, based on similarities between their characteristics in expression systems and the properties of the O2‐sensitive K+ current (IK) in pulmonary artery smooth muscle cells (PASMCs). We used gene targeting to delete Kv1.5 in mice by creating a SWAP mouse that is functionally a Kv1.5 knockout. We hypothesized that SWAP mice would display impaired HPV. The Kv1.5 α‐subunits present in the endothelium and PASMCs of wild‐type mice were absent in the lungs of SWAP mice, whereas expression of other channels Kv (1.1, 1.2, 2.1, 3.1, 4.3), Kir 3.1, Kir 6.1, and BKCa was unaltered. In isolated lungs and resistance PA rings, HPV was reduced significantly in SWAP versus wild‐type mice. Consistent with this finding, PASMCs from SWAP PAs were slightly depolarized and lacked IKv1.5, a 4‐AP and hypoxia‐sensitive component of IK that activated between ‐50 mV and ‐30 mV. We conclude that a K+ channel containing Kv1.5 α‐subunits is an important effector of HPV in mice.
Details
- Title: Subtitle
- Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage‐gated potassium channel Kv1.5
- Creators
- Stephen L Archer - University of AlbertaBarry London - University of PittsburghVaclav Hampl - Second Medical SchoolXichen Wu - University of AlbertaAli Nsair - University of AlbertaLakshmi Puttagunta - University of AlbertaKyoko Hashimoto - University of AlbertaRoss E Waite - University of AlbertaEvangelos D Michelakis - University of Alberta
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.15(10), pp.1801-1803
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fj.00-0649fje
- PMID
- 11481235
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 21
- Grant note
- National Heart, Lung, and Blood Institute (R01 HL58030) Agency of the Czech Republic (306/97/0854; 305/00/1432)
- Language
- English
- Date published
- 08/2001
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025429002771
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