Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes.
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.
Patel
A J
AJ
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Lazdunski
M
M
Honoré
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000693:Anaerobiosis; D000818:Animals; D003001:Cloning, Molecular; D051668:Delayed Rectifier Potassium Channels; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010802:Phylogeny; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D051669:Shab Potassium Channels
D051668:Delayed Rectifier Potassium Channels; C496991:Kcnb1 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D000255:Adenosine Triphosphate; D010100:Oxygen