Na(+)-Ca2+ exchange and Ca2+ depletion in rat proximal tubules

Abstract

The removal of external Ca2+ ([Ca2+]o) reduces cytosolic Ca2+ ([Ca2+]i) in rat proximal tubules. In this report the role of external Na+ ([Na+]o) on the changes of [Ca2+]i and Ca2+ efflux caused by withdrawal of [Ca2+]o is described in rat renal proximal tubules. In aequorin-loaded tubules [Ca2+]i decreased from 235 +/- 25 to 48 +/- 16 (n = 4, P = 0.017), and 45Ca2+ fractional efflux ratio (45Ca2+ FER) increased from 0.94 +/- 0.03 to 1.64 +/- 0.19 (n = 6, P = 0.021) when Ca2+ was withdrawn from the bathing media of Krebs buffer (KB). The fall of [Ca2+]i, as well as the activation of 45Ca2+ FER, was reversed when [Na+]o in Ca(2+)-free KB was lowered isosmotically from 150 to 15 mM. However, when tubules were superfused with only 5 mM [Na+]o before [Ca2+]o was removed, [Ca2+]i also declined, but 45Ca2+ FER did not increase. The Na(+)-Ca2+ exchange inhibitor dichlorobenzamil (DCB) added after [Ca2+]o was removed evoked responses similar to [Na+]o removal, although DCB also inhibited internal Ca2+ release. These results are congruous with stimulation of Na+ influx in exchange for [Ca2+]i in Ca(2+)-free KB. However, even though total tubular Na+ was higher in Ca(2+)-free KB after 10 min, the initial rate of 22Na+ influx was not different without or with [Ca2+]o.(ABSTRACT TRUNCATED AT 250 WORDS)

Mammalian Distal Tubule: Physiology, Pathophysiology, and Molecular Anatomy

“…9). Discrepancies exist between studies, some of which may be due to differences in the species examined (7,199) or the methods used (28,30,65,66,92,242,265,273).…”

Disturbed Ca2+-signaling by chloroacetaldehyde: A possible cause for chronic ifosfamide nephrotoxicity

“…Figure 6C shows a CAA-induced right shift in the dose-response curve for Na + -dependent Ca 2+ extrusion indicating that the inhibition by CAA is not due to a reduced Ca 2+ plateau, but impairment of Ca 2+ exit. Since there are contradictory data about the expression of NCX proteins in renal proximal tubule epithelial cells [23,25,26], we used RT-PCR to test whether human RPTEC show not only functional characteristics of NCX, but also express NCX-1-mRNA. Figure 7 shows the results of a representative PCR/RT-PCR for human NCX-1 protein.…”

Molecular Dissection of Ca2+ Efflux in Immortalized Proximal Tubule Cells

“…The presence of Na + /Ca 2+ exchange in proximal tubules is uncertain and controversial. Evidence supporting the presence of Na + /Ca 2+ exchange derives primarily, though not entirely, from functional studies ( Ullrich et al, 1976 ; Gmaj et al, 1979 ; Lee et al, 1980 ; Friedman et al, 1981 ; Lorenzen et al, 1984 ; Yang et al, 1988 ; Dominguez et al, 1991 , 1992 ), whereas molecular structural experiments ( Ramachandran and Brunette, 1989 ; Yu et al, 1992 ; Bourdeau et al, 1993 ; Reilly et al, 1993 ) have generally failed to confirm its presence. In the present studies we applied both a structural and functional strategy to evaluate the presence of Na + /Ca 2+ exchange in proximal tubule cells.…”