Potential role for Kv3.1b channels as oxygen sensors

Hypoxia inhibits voltage-gated K channels in pulmonary artery smooth muscle (PASM). This is thought to contribute to hypoxic pulmonary vasoconstrictio n by promoting membrane depolarization, Ca2+ influx, and contraction. Sever al of the K-channel subtypes identified in pulmonary artery have been impli cated in the response to hypoxia, but contradictory evidence clouds the ide ntity of the oxygen-sensing channels. Using patch-clamp techniques, this st udy investigated the effect of hypoxia on recombinant Kv1 channels previous ly identified in pulmonary artery (Kv1.1, Kv1.2, and Kv1.5) and Kv3.1b, whi ch has similar kinetic and pharmacological properties to native oxygen-sens itive currents. Hypoxia failed to inhibit any Kv1 channel, but it inhibited Kv3.1b channels expressed in L929 cells, as shown by a reduction of whole- cell current and single-channel activity, without affecting unitary conduct ance. Inhibition was retained in excised membrane patches, suggesting a mem brane-delimited mechanism. Using reverse transcription-polymerase chain rea ction and immunocytochemistry, Kv3.1b expression was demonstrated in PASM c ells. Moreover, hypoxia inhibited a K+ current in rabbit PASM cells in the presence of charybdotoxin and capsaicin, which preserve Kv3.1b while blocki ng most other Kv channels, but not in the presence of millimolar tetraethyl ammonium ions, which abolish Kv3.1b current. Kv3.1b channels may therefore contribute to oxygen sensing in pulmonary artery.