On the mechanism of modal regulation of cardiovascular Ca2+entry channel TRPC6

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The canonical transient receptor potential protein 6(TRPC6) is a Ca^<2+> entry channel activated by synergistic operation of receptor-mediated and mechanosentive signaling pathways. Its excessive activity contributes to the pathogenesis of cardiovascular diseases. The results of the present study suggest that the synergy between receptor and mechanical stimulations on TRPC6 channel activation likely occurs through physical interaction and functional coupling between TRPC6 channel N-terminal ankyrin-like domains and actin cytoskeleton. Further, this synergy is exaggerated by pathogenic mutations in amino acid residues adjacent to these domains, and counteracted byprotein kinase G-mediated phosphorylation of TRPC6 N-terminus, by strengthening and disrupting the N-terminus domain-actin cytoskeleton interaction, respectively.