Impaired renal calcium absorption in mice lacking calcium channel β3 subunits
Impaired renal calcium absorption in mice lacking calcium channel β3 subunits
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DOI：
10.1139/y09-035
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发表时间：
2009-07-01
影响因子：
2.1
通讯作者：
Friedman, Peter A.
中科院分区：
文献类型：
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作者：
Bernardo, Jose F.;Magyar, Clara E.;Friedman, Peter A.
使用缺乏钙通道β 3亚基（Ca-v β 3）的转基因小鼠来确定多聚体钙通道在介导刺激的肾钙吸收中的参与。我们测量了钙通道β（3）亚基缺失（Ca-v β（-/-）（3））和野生型（Ca-v β（+/+）（3））小鼠对钙保留利尿剂氯噻嗪（CTZ）增加肾脏钙吸收的能力。Ca-v β（-/-）（3）和Ca-v β（+/+）（3）小鼠的钠排泄分数控制率相当，CTZ在两组中增加钠排泄相似。CTZ仅在野生型Ca-v β（+/+）（3）小鼠中增强钙吸收。这种效应对于作用于远端小管的利尿剂是特异性的，因为Ca-v β（-/-）（3）和Ca-v β（+/+）（3）小鼠对呋塞米的反应都很小。β（3）亚基的缺失导致TrpV 5钙通道、质膜Ca-ATPase、NCX 1 Na/Ca交换蛋白和钙结合蛋白-D-9 k的代偿性增加，但不导致钙结合蛋白-D-28 k的代偿性增加。我们的结论是TrpV 5介导基础肾钙吸收，包括Ca-v β（3）的多聚体钙通道介导受刺激的钙转运。
Transgenic mice lacking calcium channel beta(3) subunits (Ca-v beta(3)) were used to determine the involvement of a multimeric calcium channel in mediating stimulated renal calcium absorption. We measured the ability of calcium channel beta(3) subunit-null (Ca-v beta(-/-)(3)) and wild-type (Ca-v beta(+/+)(3)) mice to increase renal calcium absorption in response to the calcium-sparing diuretic chlorothiazide (CTZ). Control rates of fractional sodium excretion were comparable in Ca-v beta(-/-)(3) and Ca-v beta(+/+)(3) mice and CTZ increased sodium excretion similarly in both groups. CTZ enhanced calcium absorption only in wild-type Ca-v beta(+/+)(3) mice. This effect was specific for diuretics acting on distal tubules because both Ca-v beta(-/-)(3) and Ca-v beta(+/+)(3) mice responded comparably to furosemide. The absence of beta(3) subunits resulted in compensatory increases of TrpV5 calcium channels, the plasma membrane Ca-ATPase, NCX1 Na/Ca exchanger protein, and calbindin-D-9k but not calbindin-D-28k. We conclude that TrpV5 mediates basal renal calcium absorption and that a multimeric calcium channel that includes Ca-v beta(3) mediates stimulated calcium transport.