Calcium Is Reabsorbed in the Distal Nephron and Connecting Segment, Regulated by Parathyroid Hormone, Vitamin D3, and Calcitonin
The kidney reabsorbs the majority of filtered calcium (Ca2+) and contributes significantly to the regulation of systemic Ca24 balance. Approximately 65% of filtered Ca24 is absorbed in the proximal tubule; the majority of Ca24 reabsorption in the proximal tubule is paracellular and passive, driven by electrical and chemical gradients.
Approximately 20% of filtered Ca2* is reabsorbed in the thick ascending limb of Henle’s loop. Ca24 reabsorption in this segment occurs both by passive, paracellular means, driven by electrochemical gradients, and by active, transcellular transport. Ca24 transport in the thick ascending limb is suppressed when serum Ca24 is elevated, through activation of the basolateral calcium-sensing receptor (CaSR). The distal convoluted tubule and the connecting segment reabsorb an additional 10% of the filtered Ca24, primarily by active transcellular transport. The basolateral plasma membrane of distal convoluted tubule and connecting segment cells contains a Ca24-ATPase pump that actively extrudes intracellular Ca24 into the interstitial fluid. Ca2+ is also transported across the basolateral plasma membrane by a Na4∕Ca24 antiporter that exchanges extracellular Na4 for intracellular Ca24. Ca2‘ in the tubule fluid enters the cell across the apical plasma membrane through a Ca24 channel, and diffusion to the basolateral side of the cell is facilitated by binding to a Ca2‘-binding protein, Calbindin 28k. Finally, 1% to 2% of the filtered Ca24 is reabsorbed in the collecting ducts; the mechanisms of Ca2’ transport in the collecting duct have not been determined.Regulation of Ca2+ transport occurs in the distal convoluted tubule, the connecting segment, and the cortical thick ascending limb of Henle’s loop.
Parathyroid hormone, lα,25-(OH),-vitamin D3, and calcitonin have important roles in controlling renal Ca24 excretion.Hypocalcemia (low plasma Ca24 level) stimulates parathyroid hormone release, which affects bone, the intestines, and the kidneys to raise the plasma Ca2* level. The response of the kidney occurs in the cortical thick ascending limb, the distal convoluted tubule, and the connecting segment. Parathyroid hormone (PTH) is believed to increase apical uptake of Ca2' in these segments by increasing the activity of the apical Ca24 channel. Furthermore, at least in the distal convoluted tubule, PTH increases the CΓ conductance at the basolateral plasma membrane, which hyperpolarizes the cells (the interior becomes more electrically negative) and thus increases the driving force for Ca24 entry. PTH also inhibits inorganic phosphate (P1) reabsorption in the proximal tubule by causing internalization of sodium-dependent Pj transporters (NaPi-2) in the brush border.
The hormone /a,25-(OH)2-vitamin D< is converted to its active form in the proximal convoluted tubules: this process is stimulated by PTH. Receptors for vitamin D3 are located predominantly in the distal convoluted tubule and connecting segment, where vitamin D3 increases the cellular content of the Ca2‘-binding protein, Calbindin 28k, and thus contributes to enhanced Ca24 reabsorption. Vitamin D3 also increases expression of the NaPi-2 in the proximal tubule and thus enhances phosphate reabsorption.
Calcitonin reduces the serum Ca2+ concentration, largely by stimulating Ca2f deposition in bone. Although pharmacological doses of calcitonin may enhance renal Ca2, excretion, physiological doses reduce renal Ca2* excretion. Calcitonin enhances Ca2+ reabsorption in the thick ascending limb, the distal convoluted tubule, and the connecting segment. It is believed that calcitonin hyperpolarizes cells in these segments and thereby enhances Ca2+ uptake from the tubule fluid.