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The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc.

Abstract : TRPC6 are plasma membrane cation channels. By means of live-cell imaging and spectroscopic methods, we found that HEK cells expressing TRPC6 channels (HEK-TRPC6) are enriched in zinc and sulphur and have a reduced copper content when compared to HEK cells and HEK cells expressing TRPC3 channels (HEK-TRPC3). Hence, HEK-TRPC6 cells have larger pools of mobilizable Zn2+ and are more sensitive to an oxidative stress. Synchrotron X-ray fluorescence experiments showed a higher zinc content in the nuclear region indicating that the intracellular distribution of this metal was influenced by the over-expression of TRPC6 channels. Their properties were investigated with the diacylglycerol analogue SAG and the plant extract hyperforin. Electrophysiological recordings and imaging experiments with the fluorescent Zn2+ probe FluoZin-3 demonstrated that TRPC6 channels form Zn2+-conducting channels. In cortical neurons, hyperforin-sensitive channels co-exist with voltage-gated channels, AMPA and NMDA receptors, which are known to transport Zn2+. The ability of these channels to regulate the size of the mobilizable pools of Zn2+ was compared. The data collected indicate that the entry of Zn2+ through TRPC6 channels can up-regulate the size of the DTDP-sensitive pool of Zn2+. By showing that TRPC6 channels constitute a Zn2+ entry pathway, our study suggests that they could play a role in zinc homeostasis.
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Submitted on : Thursday, January 26, 2012 - 12:54:31 PM
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Julien Gibon, Peng Tu, Sylvain Bohic, Pierre Richaud, Josiane Arnaud, et al.. The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc.. BBA - Biochimica et Biophysica Acta, Elsevier, 2011, 1808 (12), pp.2807-18. ⟨10.1016/j.bbamem.2011.08.013⟩. ⟨inserm-00663195⟩



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