Abstract
Acid-base homeostasis is crucial for numerous physiological processes. cotransporters (NBCs) belong to the solute carrier 4 (SLC4) family, which regulates intracellular pH as well as absorption and secretion. However, knowledge of the structural functions of these proteins remains limited. Electrogenic NBC (NBCe-1) is thought to be the primary factor promoting the precise acid–base equilibrium in distinct cell types for filtration and reabsorption, as well as the function of neurons and glia. NBC dysregulation is strongly linked to several diseases. As such, the need for special drugs that interfere with the transmission function of NBC is becoming increasingly urgent. In this review, we focus on the structural and functional characteristics of NBCe1, and discuss the roles of NBCe1 in the kidney, central nervous system (CNS), and related disorders, we also summarize the research on NBC inhibitors. NBCe1 and the related pathways should be further investigated, so that new medications may be developed to address the related conditions.
Highlights
Intracellular pH and extracellular pH affect almost all biological processes, including metabolism, protein synthesis and activity, ion-channel activation, neuronal excitability, and the cardiovascular system
The identical NBC isoform is expressed in both tissues, but their functions are exerted in opposite directions. In both proximal tubular kidney cells [62,63] and pancreatic cells [270,o3f61]5, NBCe1 is expressed, but acts in efflux mode in the proximal kidney tubules, whereas, due to the depolarized membrane potential caused by CFTR activation and subsequent Cl− ssuecbrseetqiounen[6t4C],l−thseecsraemtieontr[a6n4s]p, othrteersaompeertartaenssipnotrhteerionpfleurxatmesoidnetihne tihneflupxanmcroedaeticindtuhcet pcealnlsc.rFeiagtuicred4ucsthcoewllss.thFeigduifrfeer4ensthtorwansstphoertdmiffoedreesntoftrdainffseproenrtt mNBodCees1 ovfardiiafnfetsreinntthNeBpCaen1vcraeraiatinctsduinctthaendparnencraelaptircodxiumctaal ntudbruelneaclepllrso.ximal tubule cells
NBCs are associated with abnormalities in fluid regulation, central nervous system (CNS) activity, and intellectual disability
Summary
Intracellular pH (pHi) and extracellular pH (pHo) affect almost all biological processes, including metabolism, protein synthesis and activity, ion-channel activation, neuronal excitability, and the cardiovascular system. The identical NBC isoform is expressed in both tissues, but their functions are exerted in opposite directions In both proximal tubular kidney cells [62,63] and pancreatic cells [20,36], NBCe1 is expressed, but acts in efflux mode in the proximal kidney tubules, whereas, due to the depolarized membrane potential caused by CFTR activation and modes of cotransport (that is, the efflux of kidney cells and the influx of heart cells, respectively). In both proximal tubular kidney cells [62,63] and pancreatic cells [270,o3f61]5, NBCe1 is expressed, but acts in efflux mode in the proximal kidney tubules, whereas, due to the depolarized membrane potential caused by CFTR activation and subsequent Cl− ssuecbrseetqiounen[6t4C],l−thseecsraemtieontr[a6n4s]p, othrteersaompeertartaenssipnotrhteerionpfleurxatmesoidnetihne tihneflupxanmcroedaeticindtuhcet pcealnlsc.rFeiagtuicred4ucsthcoewllss.thFeigduifrfeer4ensthtorwansstphoertdmiffoedreesntoftrdainffseproenrtt mNBodCees ovfardiiafnfetsreinntthNeBpCaen1vcraeraiatinctsduinctthaendparnencraelaptircodxiumctaal ntudbruelneaclepllrso.ximal tubule cells. I overload, which initiates a series of calcium-activated cell damage processes [75,76]
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