Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
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DOI：
10.1152/ajplung.00117.2006
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发表时间：
2006-07
期刊：
影响因子：
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通讯作者：
C. Fike;M. Kaplowitz;Yongmei Zhang;J. Madden
中科院分区：
文献类型：
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作者：
C. Fike;M. Kaplowitz;Yongmei Zhang;J. Madden
本研究的目的是确定仔猪肺动脉高压早期的小肺动脉(SPA)的平滑肌细胞膜特性是否发生了改变。仔猪在室内空气(对照)和低氧条件下饲养3天。用微电极技术测量加压管状SPA(直径100~300微米)的平滑肌细胞膜电位(E(M))。测定电压门控性K(+)(K(V))通道拮抗剂4-氨基吡啶(4-AP)和K(V)1家族通道拮抗剂Correolide对SPA的反应。其他SPA用于评估K(V)1.2、K(V)1.5和K(V)2.1(免疫印迹技术)的量。E(M)在慢性低氧仔猪的SPA中的阳性率高于同龄对照仔猪的SPA。4-AP或Correolide对低氧仔猪SPA的收缩作用明显减弱。低氧仔猪SPA中K(V)1.2的丰度降低，而K(V)1.5和K(V)2.1的丰度没有变化。至少部分由于K(V)1.2的减少，在慢性缺氧性肺动脉高压的早期阶段，SPA的平滑肌细胞膜特性发生改变，导致E(M)去极化和K(V)通道家族功能受损。
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.