Dihydropyridine- and voltage-sensitive Ca2+ entry in human parathyroid cells

Abstract

Patch-clamp and fluorescence measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) were performed to directly detect extracellular Ca2+ entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo-3 AM or fluo-4 AM showed a transient increase in fluorescence (Ca2+ transient) following 10 s exposure to 150 mm K+ solution in the presence of millimolar concentrations of external Ca2+. The Ca 2+ transient was completely inactivated after 30-40 s exposure to the high-K+ solution, was reduced by dihydropyridine antagonists and was enhanced by FPL-64176, an L-type Ca2+ channel agonist. The electrophysiological and pharmacological properties of the whole-cell Ca 2+ and Ba2+ currents were similar to those of L-type Ca2+ channels. The Ca2+ transients induced by 10 s exposure to 3.0 mm extracellular Ca2+ concentration ([Ca 2+]o) were inhibited by dihydropyridine antagonists and were partly inactivated following 30-40 s exposure to the high-K+ solution. These results demonstrate, for the first time, that human parathyroid cells express L-type-like Ca2+ channels that are possibly involved in the [Ca2+]o-induced change in [Ca2+] i. This Ca2+ entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca2+-sensing receptor is poorly expressed. © 2009 The Physiological Society.