Hi everyone,

I am interested in voltage gated sodium channel currently, and I would like to ask some question to you.

As it is usually known, voltage dependency of multiple ion channels including VGNCs depend on the S4 transmembrane voltage sensor domain.

What I wonder here is, is it possible to decouple the voltage sensitivity with ion channel gating by mutating the S4 VSD?

Though Chahine et al. found that the gating membrane potential can be shifted to more positive (J. Membrane Biol. 201, 9–24 (2004)), the activity still depends on voltage.

In addition, some of ion channels with the S4 VSD are also multimodal, that is, they can be activated by other stimulation, e.g. mechanical stimulation in Nav1.5.

Thus, another question is, do you think its possible to reverse hierarchy channel activation mechanism, like making mechanosensitivity to be dominat on Nav1.5 activation.

Thank you for reading!