Activation of latent Ca2+ channels in renal epithelial cells by parathyroid hormone

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Abstract
CALCIUM has an important role in regulating epithelial cell ion transport1,2 and is itself transported by tissues involved in the maintenance of extracellular Ca2+ homeostasis3–6. Although the mechanism of Ca2+ entry in electrically excitable cells is well-documented7,8 little is known about it in epithelial cells. Calcium absorption in polarized epithelial cells is a two-step process in which Ca2+ enters cells across apical plasma membranes and is extruded across basolateral membranes9. Efflux may be mediated by an energy-dependent Ca2+-ATPase or by Na+/Ca2+ by an exchange10–12. We examined Ca2+ influx in single cultured cells from distal renal tubules sensitive to parathyroid hormone by measuring intracellular Ca2+. Our results demonstrate that parathyroid hormone activates dihydropyridine-sensitive channels responsible for Ca2+ entry. We also show that microtubule-dependent exocytosis stimulated by parathyroid hormone may be necessary for the insertion or activation of Ca2+ channels in these cells. Once inserted or activated, dihydropyridine-sensitive channels mediate Ca2+ entry into these Ca2+-transporting epithelial cells. Our results support the view that agonist-induced exocytosis may represent a general paradigm for modulation of transport in epithelial cells by delivery and incorporation of transport proteins to plasma membranes or by delivery to plasma membranes of factors regulating these proteins.