Navigating the multifaceted intricacies of the Na⁺-Cl⁻ cotransporter, a highly regulated key effector in the control of hydromineral homeostasis

Abstract

The Na+-Cl− cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as 3 splice variants in primates. Its primary role in the kidney is to mediate the cosymport of Na+ and Cl− across the apical membrane of the distal convoluted tubule. Through this role and the involvement of other ion transport systems, NCC allows the systemic circulation to reclaim a fraction of the ultrafiltered Na+, K+, Cl− and Mg+ loads in exchange for Ca2+ and HCO3−. The physiological relevance of the Na+-Cl− cotransport mechanism in human is illustrated by the several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders. The purpose of the current review is to discuss the molecular mechanisms and overall roles of Na+-Cl− cotransport as the main topics of interest. On reading the narrative proposed, one will realize that the knowledge gained in regard to these themes will continue to progress unrelentingly no matter how refined it has now become.