Identification and characteristics of a Na+/Ca2+ exchanger in cultured human mesangial cells

Menè, Paolo; Pugliese, Francesco; Faraggiana, Tullio; Cinotti, Giulio A.
December 1990
Kidney International;Dec1990, Vol. 38 Issue 6, p1199
Academic Journal
Excitable cells express Na+/Ca²+ exchange activity among other mechanisms modulating rapid fluctuations of cytosolic free Ca²+ ([Ca²+]i). We studied functions and regulation of a Na+/Ca²+ exchanger in cultured human glomerular mesangial cells. Fura-2-loaded confluent monolayers reacted to removal of ambient Na+ with an immediate, transient elevation of [Ca²+]i, assessed by single/dual wavelength fluorometry. Peak [Ca²+]i was inversely correlated with the extracellular Na+ concentration. Ca²+ influx was the sole mechanism implicated, as the [Ca²+]i, rise was prevented by EGTA. The process was inhibited by 1 mM amiloride, but not by blockers of voltage-operated Ca²+ channels. Re-addition of Na+ resulted in a rapid decrease of [Ca²+], indicating bimodal operation of the exchanger. Na+-loading the cells with monensin and ouabain enhanced Ca²+ uptake. Prior stimulation of [Ca²+]i with the thromboxane A2 mimetic, U-46619, or angiotensin II also increased Ca²+ uptake upon subsequent Na+ removal, suggesting induction of the exchanger by vasoconstrictors. Moreover, the magnitude of agonist-induced [Ca²+), transients was amplified by Na+ removal, indicating that the exchanger modulates the effects of vasoconstrictors. These results demonstrate that an inducible Na+/Ca²+ antiporter is operative in resting and stimulated human mesangial cells, further confirming their smooth muscle origin and potential regulatory role on glomerular hemodynamics.


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