Abstract
The thiazide-sensitive NaCl cotransporter (NCC, SLC12A3) is a member of the solute carrier 12 (SLC12) family of electroneutral cotransporters. NCC is expressed in the distal convoluted tubule (DCT) of the kidney, where it mediates the transport of sodium with chloride in a 1:1 stoichiometry. NCC is responsible for reabsorbing approximately 5–10 % of sodium from the glomerular filtrate. Because NCC is expressed in the distal portion of the nephron, its activity helps dictate the final sodium chloride content in the urine. Thus, it plays a key role in determining the blood pressure set point through the regulation of extracellular fluid volume. Consistent with its critical role in blood pressure and volume control, NCC is one of the major molecular targets of thiazide-type diuretics, drugs commonly used as first-line agents in the treatment of essential hypertension and edema. Since its cloning over two decades ago, much has been learned about the physiological transport properties of NCC, its regulation, and its connections to human disease. In this chapter, I provide an overview of the biology of this important cotransporter.
Keywords
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Acknowledgments
I would like to thank David Ellison and Gerardo Gamba for helpful discussions. This work was supported by grants from the NIH (R01-DK098145 and R01-HL088120), by the Pittsburgh Center for Kidney Research (P30-DK079307), and by the VA Pittsburgh Healthcare System Research Service.
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Subramanya, A.R. (2016). Thiazide-Sensitive NaCl Cotransporter. In: Hamilton, K., Devor, D. (eds) Ion Channels and Transporters of Epithelia in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3366-2_12
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