Submitted on March 29, 2006
Accepted on June 27, 2006
Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets
Candice D. Fike1*, Mark R. Kaplowitz2, Yongmei Zhang2, and Jane A. Madden3
1 Department of Pediatrics, Vanderbilt Univ. Medical Center, Nashville, Tennessee, United States; Pediatrics, Wake Forest Univ. School of Medicine, United States
2 Department of Pediatrics, Vanderbilt Univ. Medical Center, Nashville, Tennessee, United States; Pediatrics, Wake Forest Univ. School of Medicine, Winston-Salem, North Carolina, United States
3 Department of Neurology, Zablocki VA Medical Center, Milwaukee,, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: candice.fike{at}vanderbilt.edu.
Our purpose was to determine if 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 small pulmonary arteries (SPA, 100-300 microns diameter). SPA responses to the 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 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; while abundances of both Kv1.5 and Kv2.1 were unaltered in SPA from hypoxic piglets. At least partly due to 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.
