Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron
Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron
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DOI：
10.1152/ajprenal.00490.2012
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发表时间：
2012-12-01
影响因子：
4.2
通讯作者：
Sansom, Steven C.
中科院分区：
文献类型：
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作者：
Cornelius, Ryan J.;Wen, Donghai;Sansom, Steven C.
Cornelius RJ，Wen D，Hatcher LI，Sansom SC. Biclitazone promotes BK-α/β 4-mediated K excretion in the renal distal nephron.美国肾脏生理学杂志303：F1563-F1571，2012年。首次发表于2012年9月19日; doi：10.1152/ajprenal.00490.2012.-钙激活钾通道（BK），这是刺激高远端肾单位流量，在高钾条件下使用，以消除多余的K。由于BK主要与BK-β 4一起存在于酸/碱转运的嵌入细胞（IC）中，我们确定了BK-β 4敲除小鼠（β 4KO）在食用高钾碱性饮食（HK-alk）与高钾氯化物饮食（HK-Cl）时是否表现出钾排泄不足。当将野生型（WT）置于HK-alk而不是HK-Cl上时，肾BK-β 4表达增加（Western印迹）。当WT和β 4KO置于HK-Cl上时，血浆K浓度（[K]）与对照K饮食相比升高;然而，WT和β 4KO之间的K排泄没有差异。当消耗HK-alk时，与β 4KO相比，WT中的血浆[K]较低，K清除率较高。接受HK-alk的小鼠尿液呈碱性;然而，WT和β 4KO之间的尿液pH值无差异。pendrin和V-ATP酶的免疫组织化学分析显示，与WT和HK-alk上的β 4KO相比，β-IC同样增加。我们发现，与WT相比，在HK-alk上，β 4KO中钠排泄的阿米洛利敏感性降低，表明钠重吸收增强是分泌K的补偿机制。用碱性、钠缺乏、高钾饮食（LNaHK）治疗小鼠以最大限度地减少钠重吸收，这加剧了β 4KO的钾处理缺陷。当在饮用水中给予LNaHK上的WT NH 4Cl时，K排泄减少到LNaHK上的β 4KO的量级。这些结果表明，WT而不是β 4KO在HK-alk上而不是在HK-Cl上有效地分泌K，并且表明BK-alpha/β 4介导的K分泌由碳酸氢尿促进。
Cornelius RJ, Wen D, Hatcher LI, Sansom SC. Bicarbonate promotes BK-alpha/beta 4-mediated K excretion in the renal distal nephron. Am J Physiol Renal Physiol 303: F1563-F1571, 2012. First published September 19, 2012; doi: 10.1152/ajprenal.00490.2012.-Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-beta 4 in acid/base-transporting intercalated cells (IC), we determined whether BK-beta 4 knockout mice (beta 4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-beta 4 expression increased (Western blot). When WT and beta 4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and beta 4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with beta 4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and beta 4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in beta-IC, comparing WT and beta 4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in beta 4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of beta 4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of beta 4KO on LNaHK. These results show that WT, but not beta 4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-alpha/beta 4-mediated K secretion is promoted by bicarbonaturia.