The Na-Cl cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as three 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 Ca and [Formula: see text]. The physiological relevance of the Na-Cl cotransport mechanism in humans is illustrated by several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders. The purpose of the present 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381001 | PMC |
| http://dx.doi.org/10.1152/physrev.00027.2023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gitelman syndrome with diabetes and kidney stones: A case report.
Medicine (Baltimore)
January 2025
The Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, China.
Rationale: Gitelman syndrome (GS) is a rare hereditary electrolyte disorder caused by mutations in the SLC12A3 gene. There is limited literature on the role of hydrochlorothiazide (HCT) testing and the SLC12A3 single heterozygous mutation in the diagnosis and management of patients with GS. In addition, cases of GS with concomitant kidney stones are rare.
View Article and Find Full Text PDFDifferential regulation of KCC2 and NKCC1 expression by zolpidem in CA1 and CA3 hippocampal subregions of the lithium-pilocarpine status epilepticus rat model.
Exp Anim
January 2025
Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia.
Status epilepticus is linked to cognitive decline due to damage to the hippocampus, a key structure involved in cognition. The hippocampus's high vulnerability to epilepsy-related damage is the main reason for this impairment. Convulsive seizures, such as those observed in status epilepticus, can cause various hippocampal pathologies, including inflammation, abnormal neurogenesis, and neuronal death.
View Article and Find Full Text PDFInflammatory Pathways of Sulfonamide Diuretics: Insights into SLC12A Cl Symporters and Additional Targets.
Cell Physiol Biochem
January 2025
Department of Pharmacology and Toxicology, Wright State University, School of Medicine. Dayton, Ohio, United States,
Thiazide, thiazide-like, and loop diuretics are primarily known for inhibiting members of the SLC12A family of Cl transporters, which include the Na+Cl cotransporter (NCC), NaK2Cl cotransporters (NKCC1 and NKCC2) and KCl symporters (KCC1-4). While the main pharmacological effect of these diuretics is diuresis, achieved by promoting the excretion of excess water and salt through the kidneys, they have intriguing pharmacological effects beyond their traditional ones which cannot be solely attributed to their effects on renal salt transport. Of particular interest is their role in modulating inflammatory processes.
View Article and Find Full Text PDFFamilial Hyperkalemic Hypertension.
Compr Physiol
December 2024
Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
The rare disease Familial Hyperkalemic Hypertension (FHHt) is caused by mutations in the genes encoding Cullin 3 (CUL3), Kelch-Like 3 (KLHL3), and two members of the With-No-Lysine [K] (WNK) kinase family, WNK1 and WNK4. In the kidney, these mutations ultimately cause hyperactivation of NCC along the renal distal convoluted tubule. Hypertension results from increased NaCl retention, and hyperkalemia by impaired K secretion by downstream nephron segments.
View Article and Find Full Text PDFEffects of Sodium-Glucose Co-Transporter 2 Inhibitors on Serum Chloride Concentrations in Patients with Heart Failure.
J Cardiovasc Dev Dis
November 2024
Department for Cardiovascular Diseases, Dubrava University Hospital, 10000 Zagreb, Croatia.
Background And Aims: In the past few years, some reports have shown that serum chloride concentration is a more powerful prognostic predictor than serum sodium levels in heart failure (HF). Elevated Na/Cl ratio has shown to be independently associated with all-cause death in acute HF. We evaluated changes in serum chloride concentrations and Na/Cl ratio in correlation with various clinical factors during 12 months of follow-up in patients in whom SGLT2is were initiated as part of HF therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!