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

J. H. Dominguez, C. Mann, J. K. Rothrock, V. Bhati

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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45Ca2+ fractional efflux ratio (45Ca2+ FER) increased from 0.94 ± 0.03 to 1.64 ± 0.19 (n = 6, P = 0.021) when Ca2+ was withdrawn from the bathing media of Krebs buffer (KB).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 Ca2+-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 Ca2+-free KB. However, even though total tubular Na+ was higher in Ca2+-free KB after 10 min, the initial rate of 22Na+ influx was not different without or with [Ca2+]o. The enhancing effect of Ca2+-free KB on Na+ accumulation was probably attenuated by a parallel activation of Na+-K+-ATPase: in five groups of paired tubules the activity of Na+-K+-ATPase, estimated as ouabain-inhibitable O2 consumption, was higher in Ca2+-free KB than in KB (22 ± 4 and 8 ± 1 nmol O2 · mg protein-1 · min-1 at 30°C, respectively, P = 0.008). The results are consistent with the hypothesis that in tubules resting [Ca2+]i is partly dependent on Ca2+ influx and efflux, but net loss of Ca2+ is partly mediated by forward Na+Ca2+ exchange (Na+ influx for Ca2+ efflux). The homeostatic response to the loss of [Ca2+]i involves a higher rate of Ca2+ release from internal Ca2+ pools, which is also effluxed through the Na+-Ca2+ exchanger, but can be aborted if the driving force for Ca2+ efflux is removed by decreasing [Na+]o.

Original languageEnglish (US)
Pages (from-to)F328-F335
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number2 30-2
StatePublished - 1991


  • Aequorin
  • Calcium efflux
  • Cytosolic calcium

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

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