Abstract
In order to understand the function of ion channels and how it relates to their structure, we must dissect their activation in its constitutive steps (neurotransmitter binding or voltage sensing and pore opening) and measure their energy barriers. This can be done by computational analysis of single-molecule ion-channel currents, the core expertise of the LGS lab, but this technique cannot be applied to all channels. We propose to apply a new recording method (developed by MIW) to solve this problem for neuronal nicotinic receptors, a group of channels that is important for physiology and drug development.
References
- Lape Colquhoun & Sivilotti (2008) On the nature of partial agonism in the nicotinic receptor superfamily. Nature, 454, 722-7.
- Epstein, Calderhead, Girolami & Sivilotti (2016) Bayesian statistical inference in ion-channel models with exact missed event correction. Biophysical Journal 111, 333-48.
- Marabelli, Lape & Sivilotti (2015) Mechanism of activation of the prokaryotic channel ELIC by propylamine: a single-channel study. Journal of General Physiology 145,23-45.
- Weatherill & Wallace (2015) Combining single-molecule imaging and single-channel electrophysiology. Journal of Molecular Biology, 427, 146-57.
- Leptihn, Castell, Cronin, Lee, Gross, Marshall, Thompson, Holden & Wallace (2013) Constructing droplet interface bilayers from the contact of aqueous droplets in oil. Nature Protocols 8,1048-57.