Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules

J. H. Dominguez, J. G.N. Garcia, J. K. Rothrock, D. English, C. Mann

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

In the renal proximal tubule, external Ca2+ ([Ca2+](o)) is required for parathyroid hormone to elevate cytosolic Ca2+ ([Ca2+](i)). However, other hormones increase [Ca2+](i) in the absence of [Ca2+](o). These differences may arise from a diversity of signal transduction pathways acting on external and internal Ca2+ pools. However, Ca2+ influx may be necessary to expedite and maintain the rise of [Ca2+](i) for a period after the initial surge. In this study, F- was used to probe the roles of intracellular Ca2+ mobilization, Ca2+ influx, and phosphoinositide (PI) hydrolysis on the surge of [Ca2+](i) in rat proximal tubules. In the presence of external Ca2+; 1-20 mM F- evoked incremental rises of [Ca2+](i) in tubules loaded with aequorin. Whereas 10 mM F- increased [Ca2+](i) in the absence of [Ca2+](o), the time constant for the [Ca2+](i) surge was increased. These findings are consistent with a role of Ca2+ influx on the effect of F- on [Ca2+](i). Indeed, 10 mM F- also enhanced the uptake of 45Ca2+, and promoted Ca2+ influx in aequorin- and fura-2-loaded, Ca2+-deprived tubules. In tubules, F- also activated PI hydrolysis with a time course that paralleled Ca2+ mobilization. The effect of F- on [Ca2+](i) was not altered when the 39-kDa pertussis toxin substrate was inactivated with the toxin. This G protein was most likely G(i), because prostaglandin E2, an activator of G(i) in tubules, dissociated the pertussis toxin-sensitive protein. The results support the notion that activation of a signal-transduction complex, the F- substrate, causes Ca2+ influx, mobilizes internal Ca2+, and activates PI hydrolysis in rat proximal tubules. The effect on Ca2+ mobilization does not appear to be regulated by the pertussis toxin-sensitive (G(i)) protein. Although [Ca2+](o) is not necessary for the expression of the effect of F- on [Ca2+](i), Ca2+ influx may be a critical determinant for the [Ca2+](i) surge within a finite period of time.

Original languageEnglish (US)
Pages (from-to)F318-F327
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume261
Issue number2 30-2
DOIs
StatePublished - 1991

Keywords

  • Aequorin
  • Cytosolic calcium
  • Fura-2

ASJC Scopus subject areas

  • Physiology

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