Detection of dihydropyridine- and voltage-sensitive intracellular Ca2+ signals in normal human parathyroid cells

We recently showed dihydropyridine- and voltage-sensitive Ca2+ entry in cultured parathyroid cells from patients with secondary hyperparathyroidism. To determine whether normal parathyroid cells have a similar extracellular Ca2+ entry system, cells were isolated from normal (non-hyperplastic) human parathyroid glands. Fluorescence signals related to the cytoplasmic Ca2+ concentration ([Ca2+]I) were examined in these cells. Cells loaded with fluo-3/AM showed a transient increase in fluorescence (Ca2+ transient) following a 10-s exposure to a 150 mM K+ solution in the presence of millimolar concentrations of external Ca2+. The Ca2+ transient was reduced by dihydropyridine antagonists or 0.5 mM Cd2+, but enhanced by FPL-64176, an L-type Ca2+-channel agonist. Ca2+ transients induced by the 10-s exposure to 3.0 mM extracellular Ca2+ ([Ca2+]o) were also inhibited by dihydropyridine antagonists or 0.5 mM Cd2+. These results provide the first evidence that normal human parathyroid cells express a dihydropyridine-sensitive Ca2+ entry system that may be involved in the [Ca2+]o-induced change in [Ca2+]I. This system might provide a compensatory pathway for negative feedback regulation of parathyroid hormone secretion under physiological conditions.