期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 278, 期 51, 页码 51422-51432出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M309463200
关键词
-
Various cardiorespiratory diseases (e.g. congestive heart failure, emphysema) result in systemic hypoxia and patients consequently demonstrate adaptive cellular responses which predispose them to conditions such as pulmonary hypertension and stroke. Central to many affected excitable tissues is activity of large conductance, Ca2+-activated K+ (maxiK) channels. We have studied maxiK channel activity in HEK293 cells stably co-expressing the most widely distributed of the human alpha- and beta-subunits that constitute these channel following maneuvers which mimic severe hypoxia. At all [Ca2+](i), chronic hypoxia (similar to18 mm Hg, 72 h) increased K+ current density, most markedly at physiological [Ca2+](i). K+ currents in cells cultured in normoxia showed a [Ca2+](i)-dependent sensitivity to acute hypoxic inhibition (similar to25 mm Hg, 3 min). However, chronic hypoxia dramatically changed the Ca2+ sensitivity of this acute hypoxic inhibitory profile such that low [Ca2+](i) could sustain an acute hypoxic inhibitory response. Chronic hypoxia caused no change in alpha-subunit immunoreactivity with Western blotting but evoked a 3-fold increase in beta-subunit expression. These observations were fully supported by immunocytochemistry, which also suggested that chronic hypoxia augmented alpha/beta-subunit co-localization at the plasma membrane. Using a novel nuclear run-on assay and RNase protection we found that chronic hypoxia did not alter mRNA production rates or steady-state levels, which suggests that this important environmental cue modulates maxiK channel function via post-transcriptional mechanisms.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据