BACKGROUND Aldosterone activates the intercalated cell mineralocorticoid receptor, which is enhanced with hypokalemia. Whether this receptor directly regulates the intercalated cell chloride/bicarbonate exchanger pendrin is unclear, as are potassium's role in this response and the receptor's effect on intercalated and principal cell function in the cortical collecting duct (CCD). METHODS We measured CCD chloride absorption, transepithelial voltage, epithelial sodium channel activity, and pendrin abundance and subcellular distribution in wild-type and intercalated cell-specific mineralocorticoid receptor knockout mice. To determine if the receptor directly regulates pendrin, as well as the effect of serum aldosterone and potassium on this response, we measured pendrin label intensity and subcellular distribution in wild-type mice, knockout mice, and receptor-positive and receptor-negative intercalated cells from the same knockout mice. RESULTS Ablation of the intercalated cell mineralocorticoid receptor in CCDs from aldosterone-treated mice reduced chloride absorption and epithelial sodium channel activity, despite principal cell mineralocorticoid receptor expression in the knockout mice. With high circulating aldosterone, intercalated cell mineralocorticoid receptor gene ablation directly reduced pendrin's relative abundance in the apical membrane region and pendrin abundance per cell whether serum potassium was high or low. Intercalated cell mineralocorticoid receptor ablation blunted, but did not eliminate, aldosterone's effect on pendrin total and apical abundance and subcellular distribution. CONCLUSIONS With high circulating aldosterone, intercalated cell mineralocorticoid receptor ablation reduces chloride absorption in the CCD and indirectly reduces principal cell epithelial sodium channel abundance and function. This receptor directly regulates pendrin's total abundance and its relative abundance in the apical membrane region over a wide range in serum potassium concentration. Aldosterone regulates pendrin through mechanisms both dependent and independent of the IC MR receptor.

中文翻译：

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醛固酮通过血清钾中广泛的细胞盐皮质激素受体依赖性和非依赖性机制调节 Pendrin 和上皮钠通道活性。

背景醛固酮激活闰细胞盐皮质激素受体，该受体因低钾血症而增强。这种受体是否直接调节闰细胞氯化物/碳酸氢盐交换剂pendrin，钾在这种反应中的作用以及受体对皮质集合管（CCD）中闰细胞和主要细胞功能的影响尚不清楚。方法 我们测量了野生型和闰细胞特异性盐皮质激素受体敲除小鼠的 CCD 氯化物吸收、跨上皮电压、上皮钠通道活性、pendrin 丰度和亚细胞分布。为了确定受体是否直接调节 pendrin，以及血清醛固酮和钾对这种反应的影响，我们测量了野生型小鼠的 pendrin 标记强度和亚细胞分布，敲除小鼠，以及来自同一敲除小鼠的受体阳性和受体阴性闰细胞。结果 醛固酮治疗小鼠的 CCD 中闰细胞盐皮质激素受体的消融降低了氯化物吸收和上皮钠通道活性，尽管在敲除小鼠中主要细胞盐皮质激素受体表达。对于高循环醛固酮，闰细胞盐皮质激素受体基因消融直接降低了顶端膜区域的 pendrin 相对丰度和每个细胞的 pendrin 丰度，无论血清钾高还是低。闰细胞盐皮质激素受体消融减弱但并未消除醛固酮对 pendrin 总丰度和顶端丰度以及亚细胞分布的影响。结论 高循环醛固酮，闰细胞盐皮质激素受体消融降低了 CCD 中的氯离子吸收，并间接降低了主要细胞上皮钠通道的丰度和功能。该受体在血清钾浓度的广泛范围内直接调节 pendrin 的总丰度及其在顶膜区域的相对丰度。醛固酮通过依赖和独立于 IC MR 受体的机制调节 pendrin。