Renal fluid and electrolyte handling in BKCa-beta1-/- mice.
Renal fluid and electrolyte handling in BKCa-beta1-/- mice.
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发表时间：
2003
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通讯作者：
J. Pluznick;P. Wei;P. Carmines;S. Sansom
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作者：
J. Pluznick;P. Wei;P. Carmines;S. Sansom
大电导Ca（2+）激活的K（+）通道（BK（Ca））由成孔α亚基和四种辅助β亚基之一组成。β 1亚基主要存在于平滑肌中，调节BK（Ca）的Ca（2+）敏感性和药理学性质。BK（Ca）-β 1敲除小鼠（Mbeta 1（-/-））为中度高血压，与BK（Ca）在调节固有血管张力中的作用一致。由于BK（Ca）存在于各种肾细胞，包括系膜和皮质集合管，我们确定是否液体或电解质排泄受损的Mbeta 1（-/-）在等容，体积扩大，或高盐饮食条件下。在等容条件下，未发现Mbeta 1（-/-）和Mbeta 1（+/+）之间的肾功能差异。然而，肾小球滤过率（GFR）和K（+）排泄分数在Mbeta 1（-/-）对急性容量扩张的反应中显著受损。相比之下，Mbeta 1（-/-）对急性容量扩张表现出增强的Na（+）排泄和Na（+）排泄分数反应。当长期接受高盐饮食治疗时，未观察到Mbeta 1（+/+）和Mbeta 1（-/-）之间的肾功能差异。这些观察结果表明，BK（Ca）的β 1亚基有助于增加GFR，伴随着急性盐和容量负荷，并提出了它也参与调节K（+）排泄的可能性在这些条件下。
Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) are composed of pore-forming alpha-subunits and one of four accessory beta-subunits. The beta1-subunit, found predominantly in smooth muscle, modulates the Ca(2+) sensitivity and pharmacological properties of BK(Ca). BK(Ca)-beta1 null mice (Mbeta1(-/-)) are moderately hypertensive, consistent with the role of BK(Ca) in modulating intrinsic vascular tone. Because BK(Ca) are present in various renal cells including the mesangium and cortical collecting ducts, we determined whether fluid or electrolyte excretion was impaired in Mbeta1(-/-) under euvolemic, volume-expanded, or high-salt diet conditions. Under euvolemic conditions, no differences in renal function were found between Mbeta1(-/-) and Mbeta1(+/+). However, glomerular filtration rate (GFR) and fractional K(+) excretion were significantly impaired in Mbeta1(-/-) in response to acute volume expansion. In contrast, Mbeta1(-/-) exhibited enhanced Na(+) excretion and fractional Na(+) excretion responses to acute volume expansion. Differences in renal function between Mbeta1(+/+) and Mbeta1(-/-) were not observed when chronically treated with a high-salt diet. These observations indicate that the beta1-subunit of BK(Ca) contributes to the increased GFR that accompanies an acute salt and volume load and raises the possibility that it is also involved in regulating K(+) excretion under these conditions.