Abstract
The molecular structure of oxygen-sensitive delayed-rectifier K+ channels which are involved in hypoxic pulmonary artery (PA) vasoconstriction has yet to be elucidated. To address this problem, we identified the Shab K+ channel Kv2.1 and a novel Shab-like subunit Kv9.3, in rat PA myocytes. Kv9.3 encodes an electrically silent subunit which associates with Kv2.1 and modulates its biophysical properties. The Kv2.1/9.3 heteromultimer, unlike Kv2.1, opens in the voltage range of the resting membrane potential of PA myocytes. Moreover, we demonstrate that the activity of Kv2.1/Kv9.3 is tightly controlled by internal ATP and is reversibly inhibited by hypoxia. In conclusion, we propose that metabolic regulation of the Kv2.1/Kv9.3 heteromultimer may play an important role in hypoxic PA vasoconstriction and in the possible development of PA hypertension.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Amino Acid Sequence
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Anaerobiosis
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Animals
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Cloning, Molecular
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Delayed Rectifier Potassium Channels
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Ion Channel Gating
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Molecular Sequence Data
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Oxygen / pharmacology*
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Phylogeny
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Potassium Channels / classification
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Potassium Channels / drug effects
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Potassium Channels / genetics
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Potassium Channels / metabolism*
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Potassium Channels, Voltage-Gated*
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Protein Binding
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Pulmonary Artery / cytology
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Pulmonary Artery / drug effects
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Pulmonary Artery / metabolism*
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / metabolism
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Shab Potassium Channels
Substances
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Delayed Rectifier Potassium Channels
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Kcnb1 protein, rat
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Recombinant Proteins
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Shab Potassium Channels
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Adenosine Triphosphate
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Oxygen