Renal potassium transport: the pioneering studies of Gerhard Giebisch

This essay looks at the historical significance of six APS Classic Papers that are freely available on line: Malnic G, Klose RM, Giebisch G. Micropuncture study of renal potassium excretion in the rat. Am J Physiol 206: 674–686, 1964 ( http://ajplegacy.physiology.org/cgi/reprint/206/4/674 ). Malnic G, Klose RM, Giebisch G. Micropuncture study of distal tubular potassium and sodium transport in rat nephron. Am J Physiol 211: 529–547, 1966 ( http://ajplegacy.physiology.org/cgi/reprint/211/3/529 ). Malnic G, Klose RM, Giebisch G. Microperfusion study of distal tubular potassium and sodium transfer in rat kidney. Am J Physiol 211: 548–559, 1966 ( http://ajplegacy.physiology.org/cgi/reprint/211/3/548 ). Duarte CG, Chomety F, Giebisch G. Effect of amiloride, ouabain, and furosemide on distal tubular function in the rat. Am J Physiol 221: 632–640, 1971 ( http://ajplegacy.physiology.org/cgi/reprint/221/2/632 ). Malnic G, De Mello Aires M, Giebisch G. Potassium transport across renal distal tubules during acid-base disturbances. Am J Physiol 221: 1192–1208, 1971 ( http://ajplegacy.physiology.org/cgi/reprint/221/4/1192 ). Wright FS, Strieder N, Fowler NB, Giebisch G. Potassium secretion by distal tubule after potassium adaptation. Am J Physiol 221: 437–448, 1971 ( http://ajplegacy.physiology.org/cgi/reprint/221/2/437 ).

Distal tubular electrolyte transport during inhibition of renal 11β-hydroxysteroid dehydrogenase

To test the proposal that the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) confers aldosterone specificity on mineralocorticoid receptors in the distal nephron by inactivating glucocorticoids, we performed a free-flow micropuncture study of distal tubular function in adrenalectomized rats infused with high-dose corticosterone. One-half of the rats were additionally given intravenous carbenoxolone (CBX; 6 mg/h) to inhibit renal 11β-HSD activity. Although this maneuver lowered fractional Na+ excretion (1.1 ± 0.2 vs. 1.9 ± 0.2%, P < 0.01), Na+ reabsorption within the accessible distal tubule was found to be similar in the two groups of animals. In contrast, distal tubular K+ secretion was enhanced in CBX-treated rats: fractional K+ deliveries to the early and late distal collection sites in the corticosterone-alone group were 13 ± 1 and 20 ± 3%, respectively (not significant), whereas corresponding data in the CBX-treated group were 9 ± 1 and 24 ± 2% ( P < 0.01). This stimulation of distal K+ secretion provides the first direct in vivo evidence that 11β-HSD normally prevents corticosterone from exerting a mineralocorticoid-like effect in the distal tubule. The reduction in fractional Na+ excretion during inhibition of 11β-HSD, in the absence of a change in end-distal Na+delivery, suggests enhanced Na+ reabsorption in the collecting ducts.