T he cortical collecting tubule is one of the main nephron sites where mineralocorticoids and a high potassium diet modulate sodium (Na) and potassium (K) transport. In this study we explored the steroid-independent effects of a high K diet on the electrical transport properties of the isolated rabbit cortical collecting tubule principal cells. The electrophysiological analysis included transepithelial and single-cell potential measurements and equivalent circuit analysis. Rabbits were adrenalectomized (ADX) and received either a control diet (300 meq K/kg diet) or a high K diet (600 meq/kg diet) for 10 d before the experiment. The mean plasma K of ADX control animals was 6.9 mM, that of ADX animals on the high K diet 8.3 mM. The transepithelial potential difference was significantly elevated in the high K group (-3.5 mV, lumen negative), compared with ADX controls (-1.4 mV). The basolateral membrane potential in high K animals was also significantly elevated (-73 mV, cell negative, compared with -63 mV in controls). Estimates of the apical membrane partial Na and K conductances (GaNa and GaK) and of ion currents (IaNa and IaK) also demonstrated stimulation by the high K diet. In the high K group, both GaNa and GaK (0.56 and 2.67 mS.cm-2) were higher than control values (0.27 and 1.17 mS.cm-2). IaNa and IaK were also higher in high K animals (47.8 and -26.2 microA.cm-2) compared with control animals (22.4 and -11.6 microA.cm-2). Thus, a high K intake per se can induce electrophysiological changes consistent with stimulation of Na reabsorption and K secretion.