Format

Send to

Choose Destination
J Biol Chem. 2010 Oct 1;285(40):30404-10. doi: 10.1074/jbc.M110.153064. Epub 2010 Jul 23.

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

Author information

1
Department of Physiology, RWTH Aachen University, D-52074 Aachen, Germany.

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 ligand whereas mBLINaC is a constitutively open epithelial Na(+) channel.

PMID:
20656685
PMCID:
PMC2945532
DOI:
10.1074/jbc.M110.153064
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center