Sandle G I, McGlone F, Davies R J
Department of Medicine, Hope Hospital (University of Manchester School of Medicine), Salford, Great Britain.
Pflugers Arch. 1988 Jul;412(1-2):172-82. doi: 10.1007/BF00583747.
Previous in vivo studies in rat and man indicate that chronic renal insufficiency leads to an increase in the capacity of the large intestine for K secretion. The present studies were performed in isolated rat distal colon with conventional and K-sensitive microelectrodes to determine the cellular basis for enhanced colonic K secretion after 70% nephrectomy. The data revealed that in animals fed a regular diet, nephrectomy had no effect on the Na or K conductance of the apical membrane, or the kinetics of the basolateral membrane Na-K pump, but intracellular K activity decreased from 70 +/- 4 mmol/l to 58 +/- 4 mmol/l (P less than 0.005). In control (non-nephrectomised) animals, feeding a diet modestly (4-fold) enriched with K resulted in small but significant increases in the Na and K conductance of the apical membrane, no change in the kinetics of the basolateral membrane Na-K pump, and a rise in intracellular K activity from 70 +/- 4 mmol/l to 94 +/- 7 mmol/l (P less than 0.005). In contrast, in animals fed the K enriched diet, nephrectomy resulted in (i) large, amiloride-sensitive increases in transepithelial voltage and total tissue conductance (consistent with an appreciable degree of secondary hyperaldosteronism), (ii) marked increases in the Na and K conductance of the apical membrane, (iii) significant hyperpolarization of the basolateral membrane, (iv) a 100% increase (P less than 0.02) in the maximum activity of the basolateral membrane Na-K pump, and (v) a rise in intracellular K activity from 94 +/- 7 mmol/l to 129 +/- 7 mmol/l (P less than 0.0025). These data suggest that the combination of modest dietary K enrichment and 70% nephrectomy stimulated an active K secretory process which reflected an increase in the K excretory load applied to the colonic mucosa, and the effects of aldosterone. In this model of renal insufficiency, enhanced K secretion by the transcellular and paracellular (potential-dependent) pathways results in a marked rise in the K excretory capacity of the colon.
以往在大鼠和人体进行的体内研究表明，慢性肾功能不全导致大肠钾分泌能力增强。本研究采用传统微电极和钾敏感微电极，在离体大鼠远端结肠进行实验，以确定70%肾切除术后结肠钾分泌增强的细胞基础。数据显示，在喂食常规饮食的动物中，肾切除对顶端膜的钠或钾电导以及基底外侧膜钠钾泵的动力学没有影响，但细胞内钾活性从70±4 mmol/L降至58±4 mmol/L（P<0.005）。在对照（未肾切除）动物中，喂食适度（4倍）富含钾的饮食导致顶端膜钠和钾电导小幅但显著增加，基底外侧膜钠钾泵的动力学无变化，细胞内钾活性从70±4 mmol/L升至94±7 mmol/L（P<0.005）。相比之下，在喂食富含钾饮食的动物中，肾切除导致：（i）跨上皮电压和总组织电导大幅增加且对氨氯地平敏感（与明显程度的继发性醛固酮增多症一致）；（ii）顶端膜钠和钾电导显著增加；（iii）基底外侧膜显著超极化；（iv）基底外侧膜钠钾泵最大活性增加100%（P<0.02）；（v）细胞内钾活性从94±7 mmol/L升至129±7 mmol/L（P<0.0025）。这些数据表明，适度饮食补钾与70%肾切除相结合刺激了活跃的钾分泌过程，这反映了施加于结肠黏膜的钾排泄负荷增加以及醛固酮的作用。在这种肾功能不全模型中，通过跨细胞和细胞旁（电位依赖性）途径增强的钾分泌导致结肠钾排泄能力显著提高。
