Regarding your question 1: The basis of my argument of relating modal gating to conformational changes in the channel protein is the following very nice study of a potassium channel, published in
Chakrapani, S., Cordero-Morales, J., Jogini, V. et al. On the structural basis of modal gating behavior in K+ channels. Nat Struct Mol Biol 18, 67–74 (2011). https://doi.org/10.1038/nsmb.1968
- The authors study mutations of a channel that shows different modes and demonstrate that manipulating a single site restricts the channel to one mode.
- The crystal structures of the mutants are analysed and movement is simulated using molecular dynamics.
- The single-channel kinetics of individual modes is modelled using Markov models.
In summary, the study shows that the modes of the KcsA channel are associated with different conformational states.
The most closely related study in IP3 receptors might be this one:
Fan, G., Baker, M.R., Wang, Z. et al. Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating. Cell Res 28, 1158–1170 (2018). https://doi.org/10.1038/s41422-018-0108-5
Individual states of Markov models have often been interpreted as representations of conformational states, in my opinion, in most cases with little direct evidence. In contrast, I find the relationship between modes and conformational states as illustrated by Chakrapani et al. (2011) highly convincing.