Background: TRPM6 and TRPM7 combine ion channel and ␣-kinase functions. Results: ATP inhibits TRPM7 but not TRPM6 or heteromeric TRPM6/M7 channels. Disruption of phosphorylation activity of TRPM6 kinase re-establishes ATP sensitivity to heteromeric channels. Conclusion: TRPM6 uncouples heteromeric channels from cellular energy levels. Significance: The altered characteristics of TRPM6/M7 compared with homomeric TRPM7 may enhance Ca 2ϩ and Mg

We have, for the first time, demonstrated that Ca(2+) entry via endothelial TRPC3 contributes to NO release and have revealed that H-R is associated with inhibition of TRPC3 activity. Inhibition of channel trafficking to the cell surface is involved in the underlying mechanism of the decrease of TRPC3 current and the reduction in Ca(2+) entry through TRPC3 during H-R. This study suggests that TRPC3 may have the potential to be a new target for endothelial protection during H-R.