Dept. of Cellular and Integrative Physiology, Nebraska Medical Center, Omaha, NE 68198-5850, USA.
Am J Physiol Renal Physiol. 2012 Dec 1;303(11):F1563-71. doi: 10.1152/ajprenal.00490.2012. Epub 2012 Sep 19.
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-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) 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-β4 expression increased (Western blot). When WT and β4KO 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 β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, 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 β4KO. When WT on LNaHK were given NH(4)Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia.
钙激活钾通道（BK）受远曲小管高流量刺激，在高钾条件下用于排出多余的钾。由于 BK 主要与 BK-β4 一起存在于酸碱转运的闰细胞（IC）中，我们确定了在摄入高钾碱性饮食（HK-alk）与高钾氯饮食（HK-Cl）时，BK-β4 敲除小鼠（β4KO）是否表现出排钾不足。当野生型（WT）小鼠被置于 HK-alk 时，肾 BK-β4 表达增加（Western blot），但置于 HK-Cl 时则不然。当 WT 和 β4KO 被置于 HK-Cl 时，与对照 K 饮食相比，血浆 K 浓度（[K]）升高；然而，WT 和 β4KO 之间的 K 排泄没有差异。当摄入 HK-alk 时，与 β4KO 相比，WT 的血浆 [K] 更低，K 清除率更高。HK-alk 组的尿液呈碱性，但 WT 和 β4KO 之间的尿 pH 没有差异。与 HK-alk 相比，WT 和 β4KO 的β-IC 中 Pendrin 和 V-ATPase 的免疫组织化学分析均显示出相同的增加。我们发现，与 WT 相比，β4KO 上的 HK-alk 中，阿米洛利敏感的 Na 排泄减少，表明增强的 Na 重吸收是一种代偿机制，以分泌 K。用碱性、缺钠、高钾饮食（LNaHK）治疗小鼠以最小化 Na 重吸收，会夸大β4KO 缺陷的 K 处理。当 LNaHK 上的 WT 被给予饮用水中的氯化铵时，K 排泄减少到与 LNaHK 上的 β4KO 相同的程度。这些结果表明，WT 而不是 β4KO，在 HK-alk 上有效排钾，但在 HK-Cl 上则不然，并表明 BK-α/β4 介导的 K 分泌受碳酸氢盐尿的促进。
