title: Chronic hypoxia in cultured human podocytes inhibits BKCa channels by upregulating its β4-subunit.
abstract: 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.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital, Harbin Medical University, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Chang
authors.initials: C
authors.lastname: Liao
authors.forename: He
authors.initials: H
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Jia
authors.initials: J
authors.lastname: Tian
authors.forename: Shuying
authors.initials: S
authors.lastname: Dong
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jundong
authors.initials: J
authors.lastname: Jiao
mesh_terms: D015687:Cell Hypoxia; D002478:Cells, Cultured; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D021122:Protein Subunits