| First Author | Chauvet S | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1853 |
| Issue | 11 Pt A | Pages | 2957-65 |
| PubMed ID | 26348127 | Mgi Jnum | J:231400 |
| Mgi Id | MGI:5770523 | Doi | 10.1016/j.bbamcr.2015.09.004 |
| Citation | Chauvet S, et al. (2015) The Na+/K+-ATPase and the amyloid-beta peptide abeta1-40 control the cellular distribution, abundance and activity of TRPC6 channels. Biochim Biophys Acta 1853(11 Pt A):2957-65 |
| abstractText | The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Abeta(1-40), another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Abeta1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Abeta(1-40) reduced TRPC6-mediated Ca(2+) responses whereas Abeta(1-16) was ineffective. Furthermore, when Abeta(1-40) was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Abeta(1-40) which underlines the pathophysiological significance of these processes. |
