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

Abstract

CALCIUM has an important role in regulating epithelial cell ion transport^1,2 and is itself transported by tissues involved in the maintenance of extracellular Ca²⁺ homeostasis^3–6. Although the mechanism of Ca²⁺ entry in electrically excitable cells is well-documented^7,8 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 exchange^10–12. 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.