Patel A J, Lazdunski M, Honoré E
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
EMBO J. 1997 Nov 17;16(22):6615-25. doi: 10.1093/emboj/16.22.6615.
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.
参与低氧性肺动脉（PA）血管收缩的氧敏感延迟整流钾通道的分子结构尚未阐明。为了解决这个问题，我们在大鼠PA肌细胞中鉴定出了Shab钾通道Kv2.1和一个新的类Shab亚基Kv9.3。Kv9.3编码一个电沉默亚基，它与Kv2.1结合并调节其生物物理特性。与Kv2.1不同，Kv2.1/9.3异源多聚体在PA肌细胞静息膜电位的电压范围内开放。此外，我们证明Kv2.1/Kv9.3的活性受到细胞内ATP的严格控制，并被低氧可逆性抑制。总之，我们提出Kv2.1/Kv9.3异源多聚体的代谢调节可能在低氧性PA血管收缩和PA高血压的可能发展中起重要作用。
