A single amino acid tunes Ca2+ inhibition of brain liver intestine Na+ channel (BLINaC).

The Journal of Biological Chemistry
Dominik Wiemuth, Stefan Gründer

Abstract

Ion channels of the degenerin/epithelial Na(+) channel gene family are Na(+) channels that are blocked by the diuretic amiloride and are implicated in several human diseases. The brain liver intestine Na(+) channel (BLINaC) is an ion channel of the degenerin/epithelial Na(+) channel gene family with unknown function. In rodents, it is expressed mainly in brain, liver, and intestine, and to a lesser extent in kidney and lung. Expression of rat BLINaC (rBLINaC) in Xenopus oocytes leads to small unselective currents that are only weakly sensitive to amiloride. Here, we show that rBLINaC is inhibited by micromolar concentrations of extracellular Ca(2+). Removal of Ca(2+) leads to robust currents and increases Na(+) selectivity of the ion pore. Strikingly, the species ortholog from mouse (mBLINaC) has an almost 250-fold lower Ca(2+) affinity than rBLINaC, rendering mBLINaC constitutively active at physiological concentrations of extracellular Ca(2+). In addition, mBLINaC is more selective for Na(+) and has a 700-fold higher amiloride affinity than rBLINaC. We show that a single amino acid in the extracellular domain determines these profound species differences. Collectively, our results suggest that rBLINaC is opened by an unknown ...Continue Reading

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Citations

Sep 26, 2012·The Journal of General Physiology·Stefan DürrnagelStefan Gründer
Jul 12, 2013·Pflügers Archiv : European journal of physiology·Cathérine M T LefèvreDominik Wiemuth
Dec 3, 2013·Pflügers Archiv : European journal of physiology·Dominik WiemuthStefan Gründer
Sep 20, 2012·Channels·Stefan Gründer, Katrin Augustinowski
Dec 25, 2013·Channels·Dominik WiemuthStefan Gründer
Oct 21, 2016·American Journal of Physiology. Cell Physiology·Cristina MatthewmanLaura Bianchi
Apr 26, 2018·American Journal of Physiology. Cell Physiology·Cristina MatthewmanLaura Bianchi
Jun 28, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dominik WiemuthStefan Gründer
Apr 25, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Axel SchmidtGáspár Jékely
May 18, 2019·Purinergic Signalling·Axel SchmidtDominik Wiemuth
Sep 30, 2016·The Journal of Biological Chemistry·Axel SchmidtDominik Wiemuth
Jul 5, 2017·Pflügers Archiv : European journal of physiology·Akihiko FujimotoYasuo Furukawa
Sep 23, 2021·Pflügers Archiv : European journal of physiology·Shari WiegreffeDominik Wiemuth

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