Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage-gated potassium channel Kv1.5

Hypoxic pulmonary vasoconstriction (HPV) is initiated by the inhibition of several 4-aminopyridine (4-AP)-sensitive, voltage-gated, K+ channels (Kv). Several O-2-sensitive candidate channels (Kv1.2, Kv1.5, Kv2.1, and Kv3.1b) have been proposed, based on similarities between their characteristics in expression systems and the properties of the O-2-sensitive K+ current (I-K) in pulmonary artery smooth muscle cells (PASMCs). We used gene targeting t o delete Kv1.5 in mice by creating a SWAP mouse that is functionally a Kv1. 5 knockout. We hypothesized that SWAP mice would display impaired HPV. The Kv1.5 alpha -subunits present in the endothelium and PASMCs of wild-type mi ce were absent in the lungs of SWAP mice, whereas expression of other chann els Kv (1.1, 1.2, 2.1, 3.1, 4.3), Kir 3.1, Kir 6.1, and BKCa was unaltered. In isolated lungs and resistance PA rings, HPV was reduced significantly i n SWAP versus wild-type mice. Consistent with this finding, PASMCs from SWA P PAs were slightly depolarized and lacked I-Kv1.5, a 4-AP and hypoxia-sens itive component of I-K that activated between -50 mV and -30 mV. We conclud e that a K+ channel containing Kv1.5 alpha -subunits is an important effect or of HPV in mice.