Molecular basis of hypoxia-induced pulmonary vasoconstriction:: role of voltage-gated K+ channels

The hypoxia-induced membrane depolarization and subsequent constriction of small resistance pulmonary arteries occurs, in part, via inhibition of vascular smooth muscle cell voltage-gated K+ (K-v) channels open at the resting membrane potential. Pulmonary arterial smooth muscle cell K-v channel expression, antibody-based dissection of the pulmonary arterial smooth muscle cell K+ current, and the O-2 sensitivity of cloned K-v channels expressed in heterologous expression systems have all been examined to identify the molecular components of the pulmonary arterial O-2-sensitive K-v cur rent. Likely components include Kv2.1/Kv9.3 and Kv1.2/Kv1.5 heteromeric channels and the Kv3.1b alpha -subunit. Although the mechanism of K-v channel inhibition by hypoxia is unknown, it appears that K-v alpha -subunits do not sense O-2 directly. Rather, they are most likely inhibited through interaction with an unidentified O-2 sensor and/or beta -subunit. This review summarizes the role of K-v channels in hypoxic pulmonary vasoconstriction, the recent progress toward the identification of K-v channel subunits involved in this response, and the possible mechanisms of R-v channel regulation by hypoxia.