A novel synergistic stimulation of Na+-transport across frog skin (Xenopus laevis) by external Cd2+- and Ca2+-ions.

Isolated skin of the clawed frog Xenopus laevis was mounted in an Ussing-chamber. The transcellular sodium-current (INa) was identified either as amiloride-blockable (10(-3) mol/l) short-circuit current (ISC), or by correcting ISC for the shunt-current obtained with mucosal Tris. A dose of 10 mmol/l Cd2+ applied to the mucosal side increased the current by about 70%. The half-maximal effect was reached at a Cd2+-concentration of 2.6 mmol/l (in NaCl-Ringer). The quick and fully reversible effect of Cd2+ could not be seen when 10(-3) mol/l amiloride was placed in the outer, Na+-containing solution, nor when Na+ was replaced by Tris. This suggests that Cd2+ stimulates INa. Cd2+ interfered with the Na+-current self-inhibition, and therefore with the saturation of INa by increasing the apparent Michaelis constant (KNa) of this process. The "INa recline" after stepping up mucosal [Na+] was much reduced in presence of Cd2+. Ca2+-ions on the mucosal side had an identical effect to Cd2+, and 10 mmol/l Ca2+ increase INa by about 100%. The half-maximal effect was obtained with 4.4 mmol/l Ca2+. The mechanism of INa-stimulation by Ca2+ did not seem to differ from that of Cd2+. Thus, although of low Na+-transport capacity, Xenopus skin appears to be as good a model for Na+-transporting epithelia as Ranidae skin, with the exception of the calcium effect which, so far, has not been reported for Ranidae.