Active Ca2+ reabsorption in the connecting tubule

Abstract

The kidney plays a crucial role in the maintenance of the body calcium (Ca 2+ ) balance. Ca 2+ is an essential ion in all organisms and participates in a large variety of structural and functional processes. In mammals, active tubular Ca 2+ reabsorption is restricted to the distal part of the nephron, i.e., the late distal convoluted (DCT2) and the connecting tubules (CNT), where approximately 10-15% of the total Ca 2+ is reabsorbed. This active transcellular transport is hallmarked by the transient receptor potential vanilloid 5 (TRPV5) epithelial Ca 2+ channel, regulated by an array of events, and mediated by hormones, including 1,25-dihydroxyvitamin D 3 , parathyroid hormone, and estrogen. Novel molecular mechanisms have been identified, such as the direct regulatory effects of klotho and tissue kallikrein on the abundance of TRPV5 at the apical membrane. The newly discovered mechanisms could provide potential pharmacological targets in the therapy of renal Ca 2+ wasting. This review discusses the three basic molecular steps of active Ca 2+ reabsorption in the DCT/CNT segments of the nephron, including apical entry, cytoplasmic transport, and basolateral extrusion of Ca 2+ . In addition, an overview of the recently identified mechanisms governing this active Ca 2+ transport through the DCT2/CNT epithelial cells will be presented.

Cytosolic Ca2+ Buffers

“…Reported functions for CB-D28k include a role in Ca 2þ resorption in the kidney (Boros et al 2009) and modulation of insulin production and secretion in pancreatic beta cells (Reddy et al 1997;Sooy et al 1999). Data on a putative neuroprotective role against excitotoxicity have not yet resulted in a consistent picture (for a review, see Schwaller et al 2002 andSchwaller 2009).…”

PKB/SGK-Resistant GSK3 Enhances Phosphaturia and Calciuria

“…4 -10 Active calcium reabsorption is mediated by the transient receptor potential channel V5 (TRPV5) calcium channel expressed in the luminal membrane of the distal convoluted tubule and connecting tubule. [11][12][13] The expression and activity of TRPV5 is regulated by several factors similarly regulating renal phosphate transport, such as dietary calcium intake, PTH, klotho, ac-id-base status, and 1,25-(OH) 2 vitamin D 3 . [11][12][13] The role of insulin and IGF1 has remained controversial.…”

“…[11][12][13] The expression and activity of TRPV5 is regulated by several factors similarly regulating renal phosphate transport, such as dietary calcium intake, PTH, klotho, ac-id-base status, and 1,25-(OH) 2 vitamin D 3 . [11][12][13] The role of insulin and IGF1 has remained controversial. 14,15 The intracellular signaling cascades mediating the effects of these hormones on renal phosphate transporters are still incompletely understood.…”

Sodium-dependent transporters in health and disease—a special issue

“…It allows sodium to flow down its gradient across the plasma membrane in exchange for the counter transport of calcium ions. The NCX removes a single calcium ion in exchange for the import of three sodium ions [1]. The exchanger exists in the heart muscle but also in the basolateral membrane of the distal convoluted tubule in the kidney, and is considered one of the most important cellular mechanisms for removing calcium ions [1].…”