Extracellular Ca2+ regulates the stimulation of Na+ transport in A6 renal epithelia

• Published in: American journal of physiology. Renal physiology 2004-10, Vol.287 (4), p.F840-F849
• Main Authors: Jans, Danny, Simaels, Jeannine, Larivière, Els, Steels, Paul, Van Driessche, Willy
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium - pharmacology; Cell Line; Electric Conductivity; Extracellular Space - metabolism; Hypotonic Solutions - pharmacology; Magnesium - metabolism; Magnesium - pharmacology; Osmolar Concentration; Osmotic Pressure; Phospholipases A - metabolism; Phospholipases A2; Receptors, Calcium-Sensing - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Sodium - metabolism; Urothelium - cytology; Urothelium - metabolism; Water - metabolism; Xenopus laevis
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.00388.2003

We investigated the involvement of intracellular and extracellular Ca2+ in the stimulation of Na+ transport during hyposmotic treatment of A6 renal epithelia. A sudden osmotic decrease elicits a biphasic stimulation of Na+ transport, recorded as increase in amiloride-sensitive short-circuit current (Isc) from 3.4 +/- 0.4 to 24.0 +/- 1.3 microA/cm2 (n = 6). Changes in intracellular Ca2+ concentration ([Ca2+]i) were prevented by blocking basolateral Ca2+ entry with Mg2+ and emptying the intracellular Ca2+ stores before the hyposmotic challenge. This treatment did not noticeably affect the hypotonicity-induced stimulation of Isc. However, the absence of extracellular Ca2+ severely attenuated Na+ transport stimulation by the hyposmotic shock, and Isc merely increased from 2.2 +/- 0.3 to 4.8 +/- 0.7 microA/cm2. Interestingly, several agonists of the Ca2+-sensing receptor, Mg2+ (2 mM), Gd3+ (0.1 mM), neomycin (0.1 mM), and spermine (1 mM) were able to substitute for extracellular Ca2+. When added to the basolateral solution, these agents restored the stimulatory effect of the hyposmotic solutions on Isc in the absence of extracellular Ca2+ to levels that were comparable to control conditions. None of the above-mentioned agonists induced a change in [Ca2+]i. Quinacrine, an inhibitor of PLA2, overruled the effect of the agonists on Na+ transport. In conclusion, we suggest that a Ca2+-sensing receptor in A6 epithelia mediates the stimulation of Na+ transport without the interference of changes in [Ca2+]i.