Interdependence between sodium transport, external chloride, and sodium/calcium exchanger in the isolated skin of the Rana pipiens

The aim of this study was to analyze the relationship of the Na+/Ca2+ excha nger, cytosolic calcium, and chloride to the transepithelial transport of s odium in isolated frog skin. Sodium transport was measured as amiloride-inh ibitable short circuit current (SCC). We studied the effect of variations i n the concentrations of external chloride and of the manipulation of calciu m on sensitive amiloride SCC. Modifications in the movement of Ca2+ were in duced by an ionophore, A23187, and a Ca2+ channel blocker, nifedipine. Calc ium ionophore A23187 (5 and 20 muM), in a normal Ringer's solution, increas ed SCC and transepithelial potential difference (PD). In contrast, nifedipi ne (20 muM) reduced SCC and PD. The role of the Na+/Ca2+ exchanger was stud ied using dichlorobenzamil (DCB, 50 muM) and quinacrine (1 mM), inhibitors of this exchanger. They selectively increased SCC and PD on the mucosal sid e of the skin, with no effect on the serosal side. This response occurred o nly in the presence of extracellular calcium. Replacement of NaCl by sodium methanesulfonate or the addition of furosemide (1 mM) at the serosal compa rtment, decreased basal SCC and PD and blocked the response to A23187 and t he mucosal effect of DCB and quinacrine. These results suggest the presence of an Na+/Ca2+ exchanger located on the mucosal side of the frog skin, whi ch participates in the transepithelial sodium transport. The action of this exchanger may be modulated by external chloride and calcium. J. Exp. Zool. 289:23-32, 2001. (C) 2001 Wiley-Liss, Inc.