Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets

Our purpose was to determine whether smooth muscle cell membrane properties are altered in small pulmonary arteries (SPA) of piglets at an early stage of pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. A microelectrode technique was used to measure smooth muscle cell membrane potential ( Em) in cannulated, pressurized SPA (100- to 300-μm diameter). SPA responses to the voltage-gated K+ (KV) channel antagonist 4-aminopyridine (4-AP) and the KV1 family channel antagonist correolide were measured. Other SPA were used to assess amounts of KV1.2, KV1.5, and KV2.1 (immunoblot technique). Em was more positive in SPA of chronically hypoxic piglets than in SPA of comparable-age control piglets. The magnitude of constriction elicited by either 4-AP or correolide was diminished in SPA from hypoxic piglets. Abundances of KV1.2 were reduced, whereas abundances of both KV1.5 and KV2.1 were unaltered, in SPA from hypoxic piglets. At least partly because of reduced amounts of KV1.2, smooth muscle cell membrane properties are altered such that Em is depolarized and KV channel family function is impaired in SPA of piglets at an early stage of chronic hypoxia-induced pulmonary hypertension.