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 (E(m)) in cannulated, pressurized SPA (100- to 300-microm diameter). SPA responses to the voltage-gated K(+) (K(V)) channel antagonist 4-aminopyridine (4-AP) and the K(V)1 family channel antagonist correolide were measured. Other SPA were used to assess amounts of K(V)1.2, K(V)1.5, and K(V)2.1 (immunoblot technique). E(m) 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 K(V)1.2 were reduced, whereas abundances of both K(V)1.5 and K(V)2.1 were unaltered, in SPA from hypoxic piglets. At least partly because of reduced amounts of K(V)1.2, smooth muscle cell membrane properties are altered such that E(m) is depolarized and K(V) channel family function is impaired in SPA of piglets at an early stage of chronic hypoxia-induced pulmonary hypertension.
Fike
Candice D
CD
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. candice.fike@vanderbilt.edu
Kaplowitz
Mark R
MR
Zhang
Yongmei
Y
Madden
Jane A
JA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology / Q000503:physiopathology; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D012016:Reference Values; D013552:Swine
D024642:Potassium Channels, Voltage-Gated; D015761:4-Aminopyridine