Proximal tubule Na+/H+ exchanger activity in adult NHE8−/−, NHE3−/−, and NHE3−/−/NHE8−/− mice

Baum, Michel; Twombley, Katherine; Gattineni, Jyothsna; Joseph, Catherine; Wang, Lin; Zhang, Qiuyu; Dwarakanath, Vangipuram; Moe, Orson W.

doi:10.1152/ajprenal.00415.2012

Cited by 32 publications

(23 citation statements)

References 35 publications

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“…This is likely due to a compensatory upregulation of brush border NHE3 in the kidney [12]. In support of this, NHE3/NHE8 double KO mice had lower blood pressure and lower proximal tubular NHE activity compared to NHE3 KO mice.…”

Section: Slc9a8 -Nhe8mentioning

confidence: 64%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

141

122

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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Section: Slc9a8 -Nhe8mentioning

confidence: 64%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

141

122

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“…The low intracellular Na 1 is maintained by the basolateral Na 1 /K 1 -ATPase. An apical H 1 -ATPase and possibly, NHE8 under some circumstances account for the remaining portion of proximal tubule H 1 secretion and HCO 3 2 reabsorption (17)(18)(19). This H 1 -ATPase shares most subunits with the distal tubule H 1 -ATPase described below.…”

mentioning

confidence: 94%

Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

325

262

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Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

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“…The differential effects of DMA and EIPA (stimulation of insulin secretion) versus cariporide (no effect on insulin secretion) in islets described earlier could theoretically be caused by inhibition of NHE8 [6]. NHE8 knock-out mice have been generated recently and could be employed to address these questions [44,45].…”

Section: What About Other Sodium/ Hydrogen Exchangers In Islet Cells?mentioning

confidence: 99%

Role of Na/H exchange in insulin secretion by islet cells

Deisl

Albano

Fuster

2014

Current Opinion in Nephrology and Hypertension

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Purpose of review Sodium/hydrogen exchangers (NHEs) are a large family of transport proteins catalyzing the exchange of cations for protons across lipid bilayer membranes. Several isoforms are expressed in b cells of the endocrine pancreas, including the recently discovered and poorly characterized isoform NHA2. This review will summarize advances in our understanding of the roles of NHEs in the regulation of insulin secretion in b cells. Recent findingsPlasmalemmal full-length NHE1 defends b cells from intracellular acidification, but has no role in stimulussecretion coupling and is not causally involved in glucose-induced alkalinization of the b cell. The function of a shorter NHE1 splice variant, which localizes to insulin-containing large dense core vesicles, remains currently unknown. In contrast, in-vitro and in-vivo studies indicate that the NHA2 isoform is required for insulin secretion and clathrin-mediated endocytosis in b cells. SummaryRecent data highlight the importance of NHEs in the regulation of cellular pH, clathrin-mediated endocytosis and insulin secretion in b cells. Based on these studies, a pathophysiological role of NHEs in human disorders of the endocrine pancreas seems likely and should be investigated.

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Proximal tubule Na⁺/H⁺ exchanger activity in adult NHE8^−/−, NHE3^−/−, and NHE3^−/−/NHE8^−/− mice

Cited by 32 publications

References 35 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Acid-Base Homeostasis

Role of Na/H exchange in insulin secretion by islet cells

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