Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, PR China.
Biochem Biophys Res Commun. 2012 Apr 13;420(3):505-10. doi: 10.1016/j.bbrc.2012.03.021. Epub 2012 Mar 13.
Accumulating evidence suggests that podocyte hypoxia is an alternative mechanism for the pathogenesis of renal diseases. Functional, large-conductance, calcium-activated potassium channels (BK(Ca) channels) are expressed in podocytes as mechanosensitive channels; however, whether BK(Ca) channels 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% O(2) for 24 h causes a significant reduction in BK(Ca) channel currents. Molecular biology experiments showed that chronic hypoxia increased BK(Ca) channel β4-subunit mRNA and protein expression, but not the expression of the BK(Ca) pore-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 BK(Ca) channels 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.
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（BK（Ca）通道）作为机械敏感通道在足细胞中表达；然而，BK（Ca）通道是否参与足细胞对慢性缺氧的反应以及潜在的机制尚不清楚。在这里，我们使用膜片钳技术表明，将人足细胞暴露于 2%O2 24 小时会导致 BK（Ca）通道电流显著减少。分子生物学实验表明，慢性缺氧增加了 BK（Ca）通道β4 亚基 mRNA 和蛋白表达，但不增加 BK（Ca）通道孔形成α或β3 亚基的表达。此外，慢性缺氧使通道的激活范围向更去极化的电压偏移，并减缓其激活动力学，这与β4 亚基赋予的特性相似。我们得出结论，BK（Ca）通道通过上调β4 亚基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的机制提供了新的见解。
