The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport

Dorwart, Michael R.; Shcheynikov, Nikolay; Yang, Dongki; Muallem, Shmuel

doi:10.1152/physiol.00037.2007

Cited by 175 publications

(193 citation statements)

References 133 publications

(175 reference statements)

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“…Alternatively or additionally, the 20 -30 mV depolarization elicited by elevated bath [K ϩ ] may be too small to influence measurably the observed Cl Ϫ /HCO 3 Ϫ exchange activity, in contrast to the 70 -140 mV excursions applied to voltage-clamped Xenopus oocytes expressing mouse Slc26a3 and Slc26a6 (7,35). Considered in this way, the 15 mV changes in duct potential difference elicited by luminal Cl Ϫ removal and restoration in the present studies (Fig.…”

Section: Identification Of Apical CL ϫ /Hcomentioning

confidence: 75%

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Stewart

Yamamoto²,

Nakakuki³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ϫ -rich fluid in response to stimulation by the adenylyl cyclase-coupled hormone secretin. The Cl Ϫ -rich secretion of pancreatic acinar cells is modified as it flows along the pancreatic ductal system, ultimately producing pancreatic juice with final concentrations of ϳ140 mM HCO 3 Ϫ and ϳ20 mM Cl Ϫ (31). In the guinea pig pancreatic duct, the uptake of bicarbonate across the basolateral membrane is mediated by Na ϩ -HCO 3 Ϫ cotransport (NBC1) and by Na ϩ /H ϩ exchange (19). HCO 3 Ϫ efflux across the apical membrane has been proposed to be mediated by CFTR, in concert with apical Cl Ϫ /HCO 3 Ϫ exchanger activity (9). Proximal pancreatic duct HCO 3 Ϫ secretion by apical Cl Ϫ / HCO 3 Ϫ exchange is favored by the high luminal Cl Ϫ concentrations resulting from pancreatic acinar Cl Ϫ secretion. However, since this proximal fluid flows distally toward the ampullary terminus of the duct, its Cl Ϫ concentration progressively decreases in parallel with a gradual increase in its HCO 3 Ϫ concentration. These inverse changes in Cl Ϫ and HCO 3 Ϫ concentrations are predicted to alter relative contributions of apical membrane Cl Ϫ /HCO 3 Ϫ exchange and CFTR-mediated HCO 3 Ϫ conductance and have been suggested to reflect axial variation in expression and regulation of these transport activities (18). The Cl Ϫ /HCO 3 Ϫ exchangers Slc26a3 and Slc26a6 have been detected in mouse pancreatic duct and in the human pancreatic cell line CFPAC-1 (10, 22), leading to the proposal that Cl Ϫ -dependent HCO 3 Ϫ secretion by pancreatic proximal ducts represents combined activities of Slc26a6 and Slc26a3 anion exchangers, positively regulated by activated CFTR, with reciprocal positive regulation of CFTR by the anion exchangers (4, 5, 22, 23). However, a study in native mouse pancreatic duct suggests negative regulation of CFTR by Slc26a6 (43).Secretin-stimulated HCO 3 Ϫ secretion in guinea pig pancreatic duct is not dependent on elevated luminal [Cl Ϫ ] (21) (brackets denote concentration) and occurs even in the presence of luminal fluid containing 125 mM HCO 3 Ϫ and 23 mM Cl Ϫ (17). As luminal [Cl Ϫ ] falls to or below this level (with corresponding elevation of [HCO 3 Ϫ ]), CFTR Cl Ϫ permeability may fall while that for HCO 3 Ϫ may rise (34). Measurements of membrane potential (V m ) and intracellular pH (pH i ) in luminally perfused interlobular ducts from guinea pig pancreas suggest that CFTR HCO 3 Ϫ conductance can account for observed levels of stimulated bicarbonate secretion (15,18,20). A computational model of pancreatic duct HCO 3 Ϫ secretion predicted for similar conditions that ϳ94% of HCO 3 Ϫ efflux across the apical membrane was mediated by HCO 3 Ϫ conductance (36), although the model did not consider contributions from electrogenic Cl Ϫ /HCO 3 Ϫ exchange. Thus the HCO 3 Ϫ conductance of CFTR could provide the main route for apical HCO 3 Ϫ secretion in distal pancreatic ducts from species in which, like human and guinea pig, pancreatic juice contains high concentrations of HCO 3 Ϫ (ϳ140 mM). Studies of the role of SLC26-media...

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Section: Identification Of Apical CL ϫ /Hcomentioning

confidence: 75%

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Stewart

Yamamoto²,

Nakakuki³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The three-state model was also used in a recent study to better explain NLC data. 3 It was also demonstrated that with reduced chloride concentration, NLC and motility no longer fully covaried. 4 Aside from the present work, these results also imply that there are at least two voltage-dependent transition steps in the electromechanical coupling process of prestin.…”

Section: Discussionmentioning

confidence: 99%

“…The membranebased motor protein, prestin, which is a member of the solute carrier 26 anion transporter family (3), is known to be responsible for generating electromotility (4). Accompanying OHC electromotility, charge movement in the lateral membrane of the cell is observed.…”

Section: Electromotility (1) Of Mammalian Cochlear Outer Hair Cells (mentioning

confidence: 99%

Evidence That Prestin Has at Least Two Voltage-dependent Steps

Homma

Dallos

2011

Journal of Biological Chemistry

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Prestin is a voltage-dependent membrane-spanning motor protein that confers electromotility on mammalian cochlear outer hair cells, which is essential for normal hearing of mammals. Voltage-induced charge movement in the prestin molecule is converted into mechanical work; however, little is known about the molecular mechanism of this process. For understanding the electromechanical coupling mechanism of prestin, we simultaneously measured voltage-dependent charge movement and electromotility under conditions in which the magnitudes of both charge movement and electromotility are gradually manipulated by the prestin inhibitor, salicylate. We show that the observed relationships of the charge movement and the physical displacement (q-d relations) are well represented by a three-state Boltzmann model but not by a two-state model or its previously proposed variant. Here, we suggest a molecular mechanism of prestin with at least two voltage-dependent conformational transition steps having distinct electromechanical coupling efficiencies.Electromotility (1) of mammalian cochlear outer hair cells (OHCs) 2 is a rapid voltage-induced force-generating cell length change that is indispensable for the frequency selectivity and sensitivity of mammalian hearing (2). The membranebased motor protein, prestin, which is a member of the solute carrier 26 anion transporter family (3), is known to be responsible for generating electromotility (4). Accompanying OHC electromotility, charge movement in the lateral membrane of the cell is observed. This charge movement is manifested in the bell-shaped voltage-dependent cell membrane capacitance, which is often referred to as nonlinear capacitance (NLC) (5, 6)).The question of how prestin functions as a membranebased molecular motor has received a great deal of attention; however, even some fundamental issues are still obscure. To understand the mode of operation of the molecule, the relationship between charge movement, which initiates conformational change, and motor function needs to be quantified. However, only minimal attempts have been made to this effect (6, 7). Under normal operating circumstances NLC data are usually well explained by the simple two-state Boltzmann model with an apparent valency of charge of less than unity. Interesting theoretical work suggested that three-or higher-state models might provide superior description of the process (8, 9). In some work three-state fits were dictated by the data (10). To explain some properties of NLC at extreme membrane voltages, a modified two-state model has also been proposed (11). However, those models have not been subjected to rigorous examination as to their generality under various experimental conditions. It is one purpose of the present work to provide such an examination. We find that a Boltzmann model with at least two voltage-dependent steps is required for explaining prestin function.Since the discovery of prestin, assessments of effects of mutations and drugs on its function have become readily feasible using heter...

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“…The Slc26 family of multifunctional anion exchanger proteins is believed to handle oxalate in mammalian organs (92)(93)(94)(95)) and a few specific members of this family may play a key role in the aetiology of hyperoxaluria and oxalate urolithiasis. Three organs, the intestine as an absorbing organ, liver as a metabolic organ, and kidneys as the main secretory organ, are major players in handling oxalate in the organism.…”

Section: Oxalate-handling Transporters and Their Role In Hyperoxalurimentioning

confidence: 99%

Oxalate: From the Environment to Kidney Stones

Brzica

Breljak

Burckhardt

et al. 2013

Archives of Industrial Hygiene and Toxicology

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Oxalate urolithiasis (nephrolithiasis) is the most frequent type of kidney stone disease. Epidemiological research has shown that urolithiasis is approximately twice as common in men as in women, but the underlying mechanism of this sex-related prevalence is unclear. Oxalate in the organism partially originate from food (exogenous oxalate) and largely as a metabolic end-product from numerous precursors generated mainly in the liver (endogenous oxalate). Oxalate concentrations in plasma and urine can be modifi ed by various foodstuffs, which can interact in positively or negatively by affecting oxalate absorption, excretion, and/or its metabolic pathways. Oxalate is mostly removed from blood by kidneys and partially via bile and intestinal excretion. In the kidneys, after reaching certain conditions, such as high tubular concentration and damaged integrity of the tubule epithelium, oxalate can precipitate and initiate the formation of stones. Recent studies have indicated the importance of the SoLute Carrier 26 (SLC26) family of membrane transporters for handling oxalate. Two members of this family [Sulfate Anion Transporter 1 (SAT-1; SLC26A1) and Chloride/Formate EXchanger (CFEX; SLC26A6)] may contribute to oxalate transport in the intestine, liver, and kidneys. Malfunction or absence of SAT-1 or CFEX has been associated with hyperoxaluria and urolithiasis. However, numerous questions regarding their roles in oxalate transport in the respective organs and male-prevalent urolithiasis, as well as the role of sex hormones in the expression of these transporters at the level of mRNA and protein, still remain to be answered.

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The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport

Cited by 175 publications

References 133 publications

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Evidence That Prestin Has at Least Two Voltage-dependent Steps

Oxalate: From the Environment to Kidney Stones

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The Solute Carrier 26 Family of Proteins in Epithelial Ion Transport

Cited by 175 publications

References 133 publications

Functional coupling of apical Cl−/HCO3− exchange with CFTR in stimulated HCO3− secretion by guinea pig interlobular pancreatic duct

Functional coupling of apical Cl−/HCO3− exchange with CFTR in stimulated HCO3− secretion by guinea pig interlobular pancreatic duct

Evidence That Prestin Has at Least Two Voltage-dependent Steps

Oxalate: From the Environment to Kidney Stones

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Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct

Functional coupling of apical Cl⁻/HCO₃⁻ exchange with CFTR in stimulated HCO₃⁻ secretion by guinea pig interlobular pancreatic duct