CALCIUM AND MAGNESIUM - LOW PASSIVE PERMEABILITY AND TUBULAR SECRETION IN THE MOUSE MEDULLARY THICK ASCENDING LIMB OF HENLES LOOP (MTAL)

Recent studies from our laboratory have shown that in the mouse and ra t nephron Ca2+ and Mg2+ are not reabsorbed in the medullary part of th e thick ascending limb (mTAL) of Henle's loop. The aim of the present study was to investigate whether the absence of transepithelial Ca2+ a nd Mg2+ transport in the mouse mTAL is due to its relative low permeab ility to divalent cations. For this purpose, transepithelial ion net f luxes were measured by electron probe analysis in isolated perfused mo use mTAL segments, when the transepithelial potential difference (PDte .) was varied by chemical voltage clamp, during active NaCl transport inhibition by luminal furosemide. The results show that transepithelia l Ca2+ and Mg2+ net fluxes in the mTAL are not driven by the transepit helial PDte. At zero voltage, a small but significant net secretion of Ca2+ into the tubular lumen was observed. With a high lumen-positive PDte generated by creating a transepithelial bath-to-lumen NaCl concen tration gradient, no Ca2+ and Mg2+ reabsorption was noted; instead sig nificant and sustained Ca2+ and Mg2+ net secretion occurred. When a lu men-positive PDte was generated in the absence of apical furosemide, b ut in the presence of a transepithelial bath-to-lumen NaCl concentrati on gradient, a huge Ca2+ net secretion and a lesser Mg2+ net secretion , not modified by ADH, were observed. Replacement of Na+ by K+ in the lumen perfusate induced, in the absence of PDte changes, important but reversible net secretions of Ca2+ and Mg2+. In conclusion, our result s indicate that the passive permeability of the mouse mTAL to divalent cations is very low and not influenced by ADH. This nephron segment c an secrete Ca2+ and Mg2+ into the luminal fluid under conditions which elicit large lumen-positive transepithelial potential differences. Gi ven the impermeability of this epithelium to Ca2+ and Mg2+, the secret ory processes would appear to be of cellular origin.