The role of twin pore domain and other K+ channels in hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction (HPV) describes the vasoconstrictor response of pulmonary arteries to hypoxia, which directs blood flow towards better ventilated areas of the lung. Exactly how pulmonary arteries sense oxygen and mediate this response is widely debated and several hypotheses have emerged. One has smooth muscle K+ channels as the primary O2 sensor, hypoxia causing K+ channel inhibition, membrane depolarization and voltage-dependent Ca2+ influx. Even if this mechanism is not the primary response of pulmonary arteries to hypoxia, inhibition of K+ channel activity probably plays a role in HPV, due to enhanced membrane excitability and Ca2+ influx. Hypoxia inhibits several different K+ channels expressed in pulmonary artery smooth muscle, most from the K(v) class of voltage-gated K+ channels, but the properties of many K(v) channels are incompatible with a role in initiating HPV. Twin-pore domain K+ channels have emerged as prime candidates for controlling the resting membrane potential of cells. The identification of the twin-pore channel, TASK, in pulmonary artery smooth muscle, along with reports that it is inhibited by hypoxia, raises the possibility that a member of this family of channels acts as an O2 sensor in pulmonary artery. An unidentified low-threshold, voltage-dependent K+ channel might also contribute.