Chronic hypoxia in cultured human podocytes inhibits BKCa channels by upregulating its β4-subunit.
Chronic hypoxia in cultured human podocytes inhibits BKCa channels by upregulating its β4-subunit.
复制标题
DOI：
10.1016/j.bbrc.2012.03.021
复制
发表时间：
2012-04
影响因子：
3.1
通讯作者：
Rui Zhang;Hui Sun;C. Liao;He Yang;Bo Zhao;Jia-Nan Tian;S. Dong;Zhiren Zhang;Jundong Jiao
中科院分区：
文献类型：
--
作者：
Rui Zhang;Hui Sun;C. Liao;He Yang;Bo Zhao;Jia-Nan Tian;S. Dong;Zhiren Zhang;Jundong Jiao
越来越多的证据表明足细胞缺氧是肾脏疾病发病机制的另一种机制。功能性大电导钙激活钾通道 (BKCachannels) 在足细胞中表达为机械敏感通道；然而，BKCa通道是否参与足细胞对慢性缺氧的反应以及可能的潜在机制仍不清楚。在这里，我们使用膜片钳技术证明，将人类足细胞暴露于 2% O2 24 小时会导致 BKCa 通道电流显着降低。分子生物学实验表明，慢性缺氧会增加 BKCa 通道 β4 亚基 mRNA 和蛋白质的表达，但不会增加 BKCapore 形成 α 或 β3 亚基的表达。此外，慢性缺氧使通道激活范围转向更去极化的电压并减慢其激活动力学，这与 β4 亚基赋予的特性相似。我们得出结论，BKCa 通道通过 β4 亚基的上调参与足细胞对慢性缺氧的反应。这些发现为足细胞对缺氧的细胞反应机制提供了新的见解。
Accumulating evidence suggests that podocyte hypoxia is an alternative mechanism for the pathogenesis of renal diseases. Functional, large-conductance, calcium-activated potassium channels (BKCachannels) are expressed in podocytes as mechanosensitive channels; however, whether BKCachannels are involved in the podocyte response to chronic hypoxia and the possible underlying mechanisms remain unclear. Here, we use the patch clamp technique to show that the exposure of human podocytes to 2% O2for 24h causes a significant reduction in BKCachannel currents. Molecular biology experiments showed that chronic hypoxia increased BKCachannel β4-subunit mRNA and protein expression, but not the expression of the BKCapore-forming α- or β3-subunits. Furthermore, chronic hypoxia shifted the channel activation range toward more depolarized voltages and slowed its activation kinetics, which are similar to the properties conferred by the β4-subunit. We conclude that BKCachannels are involved in the response of podocytes to chronic hypoxia via the upregulation of the β4-subunit. These findings provide new insight into the mechanism underlying the cellular responses of podocytes to hypoxia.