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NHA2 is expressed in distal nephron and regulated by dietary sodium

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Abstract

Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na+(Li+)/H+ antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H+-coupled Na+(Li+) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2. In murine kidney sections, NHA2 localized apically to distal convoluted (both DCT1 and 2) and connecting tubules, partially overlapping in distribution with V-ATPase, AQP2, and NCC1 transporters. Mice fed a diet high in sodium chloride showed elevated transcripts and expression of NHA2 protein. We propose a model in which NHA2 plays a dual role in salt reabsorption or secretion, depending on the coupling ion (sodium or protons). The identified novel regulation of Na+/H+ antiporter in the kidney suggests new roles in salt homeostasis and disease.

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Abbreviations

DCT:

Distal convoluted tubule

NCC:

Sodium chloride cotransporter

CNT:

Connecting tubule (CNT)

AQP2:

Aquaporin 2

CPA:

Cation proton antiporter

CCD:

Cortical collecting duct

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Acknowledgements

This work was supported by grants from the National Institutes of Health R01 DK108304 (to R.R.), DK081610 (J.L.P.), Canadian Institute of Health Research (R.T.A.), and University of Michigan-Dearborn startup funds (KCK).

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Authors and Affiliations

  1. Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA

    Kalyan C. Kondapalli, Jennifer L Pluznick & Rajini Rao

  2. Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Road, Dearborn, MI, 48128, USA

    Kalyan C. Kondapalli

  3. Division of Nephrology, Department of Pediatrics, University of Alberta, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada

    R. Todd Alexander

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  1. Kalyan C. Kondapalli
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  2. R. Todd Alexander
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  3. Jennifer L Pluznick
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  4. Rajini Rao
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Correspondence to Rajini Rao.

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Kondapalli, K.C., Todd Alexander, R., Pluznick, J.L. et al. NHA2 is expressed in distal nephron and regulated by dietary sodium. J Physiol Biochem 73, 199–205 (2017). https://doi.org/10.1007/s13105-016-0539-8

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  • DOI: https://doi.org/10.1007/s13105-016-0539-8

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