THE MINERALOCORTICOID ALDOSTERONE ACTIVATES A PROTON CONDUCTANCE IN CULTURED KIDNEY-CELLS

The mineralocorticoid aldosterone is the most important hormone for th e regulation of Na+ and K+ homeostasis in mammals and is thereby invol ved in the regulation of extracellular volume and blood pressure. Beca use aldosterone is a steroid hormone, the classical way of action invo lves transcription, translation, and protein synthesis. We previously reported a rapid, nongenomic, and Zn2+-sensitive action of aldosterone on Na+/H+ exchange in renal epithelial [Madin-Darby canine kidney (MD CK)] cells (M. Gekle, N. Golenhofen, H. Oberleithner, and S. Silbernag l. Proc. Natl. Acad. Sci. 93: 10500-10504, 1996). Here we show that, i n the absence of Na+ (i.e., with inactive Na+/H+ exchange), aldosteron e induces a membrane potential-dependent and Zn2+-sensitive cytoplasmi c acidification in MDCK cells within 2-4 min. This aldosterone-induced activation of a proton conductance is insensitive to the inhibitor of the classical genomic pathway, spironolactone. Furthermore, the inhib itor of serine/threonine kinases and staurosporine, as well as the spe cific inhibitor of protein kinase C (PKC), calphostin C, prevented pro ton conductance activation. Activation of PKC by phorbol esters mimick ed the effect of aldosterone. Furthermore, preincubation of the cells with pertussis toxin reduced the effect of aldosterone significantly. We propose a new nongenomic mechanism of action for aldosterone, indep endently of the intracellular type 1 mineralocorticoid receptor: G pro tein-dependent stimulation of PKC by aldosterone leads to the activati on of a plasma membrane proton conductance that enhances the activity of Na+/H+ exchange. This rapid nongenomic effect could explain the obs ervation that aldosterone may alter renal Na+ and K+ excretion within 5-10 min.