Optoelectrical dynamics of ion channels and subcellular calcium nanodomains

Résumé

Countless investigations have used highly invasive electrophysiology or non-dynamic biochemical approaches to study synapses and networks. Optogenetic approaches, combined with imaging techniques, are revolutionary tools to excite specific live cells and detect the activity of signaling molecules in populations of neurons. However, refinement of current optical methods is needed, due to the lack of molecular or spatial specificity. This refinement is particularly important for imaging Ca2+ in neurons, since Ca2+ sig- nals exert their highly specific functions in well-defined cellular subcompartments. Coupling of Ca2+ signaling to membrane voltage occurs in Ca2+ nanodomains where Ca2+ influx through voltage-gated Ca2+ channels is located within 10-50 nm of BK K+ channels. Upon Ca2+ entry, BK open in response to additive effects of Ca2+ and volt- age to limit neuronal excitability. Nevertheless, much remains to be known about this process, since currently no sensors located specifically to these regions are avail- able. Developing probes that provide bright readouts in vivo combined with ex- tremely fast and high spatial resolution imaging systems is crucial to progress to- wards our knowledge about neuronal networking.