Influence of the in vivo calcium status on cellular calcium homeostasis and the level of the calcium-binding protein calreticulin in rat hepatocytes

Little attention has been given to the consequences of the in vivo calcium status on intracellular calcium homeostasis despite several pathological st ates induced by perturbations of the in vivo calcium balance. The aim of th ese studies was to probe the influence of an in vivo calcium deficiency on the resting cytoplasmic Ca2+ concentration and the inositol-1,4,5-trisphosp hate-sensitive Ca2+ pools. Studies were conducted in hepatocytes (a cell ty pe well characterized for its cellular Ca2+ response) isolated from normal and calcium-deficient rats secondary to vitamin D depletion. Both resting c ytoplasmic Ca2+ concentration and Ca2+ mobilization from inositol-1,4,5-tri sphosphate -sensitive cellular pools were significantly lowered by calcium depletion. In addition, Ca deficiency was shown to significantly reduce cal reticulin messenger RNA and protein levels but calcium entry through store- operated calcium channels remained unaffected, indicating that the Ca2+ ent ry mechanisms are still fully operational in calcium deficiency. The effect s of calcium deficiency on cellular calcium homeostasis were reversible by repletion with oral calcium feeding alone or by the administration of the c alcium-regulating hormone 1,25-dihydroxyvitamin D,, further strengthening t he tight link between extra- and intracellular calcium. These data, therefo re, challenge the currently prevailing hypothesis that extracellular Ca2+ h as no significant impact on cellular Ca2+ by demonstrating that despite the large Ca2+ gradient between extra- and intracellular Ca2+ concentrations, calcium deficiency in vivo significantly alters the hormone-sensitive cellu lar calcium homeostasis.