NHE8 is an intracellular cation/H<sup>+</sup>exchanger in renal tubules of the yellow fever mosquito<i>Aedes aegypti</i>

Piermarini, Peter M.; Weihrauch, Dirk; Meyer, Heiko; Huss, Markus; Beyenbach, Klaus W.

doi:10.1152/ajprenal.90564.2008

Cited by 49 publications

(23 citation statements)

References 94 publications

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“…From its gene sequence, NHE8 is predicted to be an intracellular NHE isoform, and it shares relatively little sequence similarity with other mammalian NHEs (16,32,33). Indeed, NHE8 is an intracellular NHE in the mosquito Malpighian tubule (34). In mammals, NHE8 has been localized to the Golgi where it likely plays a role in pH regulation and ionic composition (32).…”

Section: Discussionmentioning

confidence: 99%

Effect of metabolic acidosis on neonatal proximal tubule acidification

Twombley

Gattineni²,

Bobulescu³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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The serum bicarbonate in neonates is lower than adults due in large part to a lower rate of proximal tubule acidification. It is unclear if the neonatal proximal tubule is functioning at maximal capacity or if the proximal tubule can respond to metabolic acidosis as has been described in adult proximal tubules. We find that neonatal mouse brush-border membranes have a lower Na(+)/H(+) exchanger (NHE) 3 protein abundance (neonate 0.11 ± 0.05 vs. adult 0.64 ± 0.07; P < 0.05) and a higher NHE8 protein abundance (neonate 1.0 ± 0.01 vs. adult 0.13 ± 0.09; P < 0.001) compared with adults. To examine if neonates can adapt to acidosis, neonatal mice were gavaged with either acid or vehicle for 4 days, resulting in a drop in serum bicarbonate from 19.5 ± 1.0 to 8.9 ± 0.6 meq/l (P < 0.001). Proximal convoluted tubule Na(+)/H(+) exchanger activity (dpH(i)/dt) was 1.68 ± 0.19 pH units/min in control tubules and 2.49 ± 0.60 pH units/min in acidemic neonatal mice (P < 0.05), indicating that the neonatal proximal tubule can respond to metabolic acidosis with an increase in Na(+)/H(+) exchanger activity. Similarly, brush-border membrane vesicles from neonatal rats had an increase in Na(+)/H(+) exchanger activity with acidemia that was almost totally inhibited by 10(-6) M 5-(N-ethyl-n-isopropyl)-amiloride, a dose that has little effect on NHE3 but inhibits NHE8. There was a significant increase in both NHE3 (vehicle 0.35 ± 0.07 vs. acid 0.73 ± 0.07; P < 0.003) and NHE8 brush-border membrane protein abundance (vehicle 0.41 ± 0.05 vs. acid 0.73 ± 0.06; P < 0.001) in acidemic mouse neonates compared with controls. A comparable increase in NHE3 and NHE8 was found in neonatal rats with acidosis. In conclusion, the neonatal proximal tubule can adapt to metabolic acidosis with an increase in Na(+)/H(+) exchanger activity.

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Section: Discussionmentioning

confidence: 99%

Effect of metabolic acidosis on neonatal proximal tubule acidification

Twombley

Gattineni²,

Bobulescu³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…They proposed that 'AeNHE8 may be coupled to the inward H + gradient across the Malpighian tubules and plays a role in the extrusion of excess sodium and potassium…'. However, Piermarini et al were not able to confirm the apical localization in Malpighian tubules (Piermarini et al, 2009). …”

Section: Genomes To the Rescuementioning

confidence: 94%

“…aegypti adult Malpighian tubules, Piermarini, Beyenbach and associates were able to work around the pitfalls of an endogenous conductance that is activated by xenic cRNA and showed that AeNHE8 is an endosomal transporter (Piermarini et al, 2009). Using quantitative PCR (qPCR) and immunohistochemistry they showed that AeNHE8 is widely distributed in adult mosquito tissues and not especially prominent in Malpighian tubules.…”

Section: Mosquito Nhes Are Not Electrophoretic Plasma Membrane Proteinsmentioning

confidence: 99%

Voltage coupling of primary H+ V-ATPases to secondary Na+- or K+-dependent transporters

Harvey

2009

Journal of Experimental Biology

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SUMMARY This review provides alternatives to two well established theories regarding membrane energization by H+ V-ATPases. Firstly, we offer an alternative to the notion that the H+ V-ATPase establishes a protonmotive force (pmf) across the membrane into which it is inserted. The term pmf, which was introduced by Peter Mitchell in 1961 in his chemiosmotic hypothesis for the synthesis of ATP by H+ F-ATP synthases, has two parts, the electrical potential difference across the phosphorylating membrane, Δψ, and the pH difference between the bulk solutions on either side of the membrane, ΔpH. The ΔpH term implies three phases – a bulk fluid phase on the H+ input side, the membrane phase and a bulk fluid phase on the H+ output side. The Mitchell theory was applied to H+ V-ATPases largely by analogy with H+ F-ATP synthases operating in reverse as H+ F-ATPases. We suggest an alternative, voltage coupling model. Our model for V-ATPases is based on Douglas B. Kell's 1979 `electrodic view' of ATP synthases in which two phases are added to the Mitchell model – an unstirred layer on the input side and another one on the output side of the membrane. In addition, we replace the notion that H+ V-ATPases normally acidify the output bulk solution with the hypothesis, which we introduced in 1992, that the primary action of a H+ V-ATPase is to charge the membrane capacitance and impose a Δψ across the membrane; the translocated hydrogen ions (H+s) are retained at the outer fluid–membrane interface by electrostatic attraction to the anions that were left behind. All subsequent events, including establishing pH differences in the outside bulk solution, are secondary. Using the surface of an electrode as a model, Kell's`electrodic view' has five phases – the outer bulk fluid phase, an outer fluid–membrane interface, the membrane phase, an inner fluid–membrane interface and the inner bulk fluid phase. Light flash,H+ releasing and binding experiments and other evidence provide convincing support for Kell's electrodic view yet Mitchell's chemiosmotic theory is the one that is accepted by most bioenergetics experts today. First we discuss the interaction between H+ V-ATPase and the K+/2H+ antiporter that forms the caterpillar K+ pump, and use the Kell electrodic view to explain how the H+s at the outer fluid–membrane interface can drive two H+ from lumen to cell and one K+ from cell to lumen via the antiporter even though the pH in the bulk fluid of the lumen is highly alkaline. Exchange of outer bulk fluid K+ (or Na+) with outer interface H+ in conjunction with (K+ or Na+)/2H+ antiport, transforms the hydrogen ion electrochemical potential difference, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{{\mu}}_{\mathrm{H}}\) \end{document}, to a K+electrochemical potential difference, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{{\mu}}_{\mathrm{K}}\) \end{document} or a Na+electrochemical potential difference, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{{\mu}}_{\mathrm{Na}}\) \end{document}. The \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{{\mu}}_{\mathrm{K}}\) \end{document} or \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\overline{{\mu}}_{\mathrm{Na}}\) \end{document} drives K+- or Na+-coupled nutrient amino acid transporters (NATs), such as KAAT1(K+ amino acid transporter 1), which moves Na+ and an amino acid into the cell with no H+s involved. Examples in which the voltage coupling model is used to interpret ion and amino acid transport in caterpillar and larval mosquito midgut are discussed.

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“…Defolliculated Xenopus laevis oocytes (Ecocyte Bioscience, Asutin, TX) were injected with 10 ng of Ae Kir1 or Ae Kir2B cRNA and cultured for 3–7 days at 18°C in OR3 media [14], [15].…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Validation of an Inward-Rectifier Potassium (Kir) Channel as an Insecticide Target in the Yellow Fever Mosquito Aedes aegypti

et al. 2014

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Mosquitoes are important disease vectors that transmit a wide variety of pathogens to humans, including those that cause malaria and dengue fever. Insecticides have traditionally been deployed to control populations of disease-causing mosquitoes, but the emergence of insecticide resistance has severely limited the number of active compounds that are used against mosquitoes. Thus, to improve the control of resistant mosquitoes there is a need to identify new insecticide targets and active compounds for insecticide development. Recently we demonstrated that inward rectifier potassium (Kir) channels and small molecule inhibitors of Kir channels offer promising new molecular targets and active compounds, respectively, for insecticide development. Here we provide pharmacological validation of a specific mosquito Kir channel (AeKir1) in the yellow fever mosquito Aedes aegypti. We show that VU590, a small-molecule inhibitor of mammalian Kir1.1 and Kir7.1 channels, potently inhibits AeKir1 but not another mosquito Kir channel (AeKir2B) in vitro. Moreover, we show that a previously identified inhibitor of AeKir1 (VU573) elicits an unexpected agonistic effect on AeKir2B in vitro. Injection of VU590 into the hemolymph of adult female mosquitoes significantly inhibits their capacity to excrete urine and kills them within 24 h, suggesting a mechanism of action on the excretory system. Importantly, a structurally-related VU590 analog (VU608), which weakly blocks AeKir1 in vitro, has no significant effects on their excretory capacity and does not kill mosquitoes. These observations suggest that the toxic effects of VU590 are associated with its inhibition of AeKir1.

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NHE8 is an intracellular cation/H⁺exchanger in renal tubules of the yellow fever mosquitoAedes aegypti

Cited by 49 publications

References 94 publications

Effect of metabolic acidosis on neonatal proximal tubule acidification

Effect of metabolic acidosis on neonatal proximal tubule acidification

Voltage coupling of primary H+ V-ATPases to secondary Na+- or K+-dependent transporters

Pharmacological Validation of an Inward-Rectifier Potassium (Kir) Channel as an Insecticide Target in the Yellow Fever Mosquito Aedes aegypti

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NHE8 is an intracellular cation/H+exchanger in renal tubules of the yellow fever mosquitoAedes aegypti

Cited by 49 publications

References 94 publications

Effect of metabolic acidosis on neonatal proximal tubule acidification

Effect of metabolic acidosis on neonatal proximal tubule acidification

Voltage coupling of primary H+ V-ATPases to secondary Na+- or K+-dependent transporters

Pharmacological Validation of an Inward-Rectifier Potassium (Kir) Channel as an Insecticide Target in the Yellow Fever Mosquito Aedes aegypti

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NHE8 is an intracellular cation/H⁺exchanger in renal tubules of the yellow fever mosquitoAedes aegypti