Relation between ligand binding and activation gating in nicotinic acetylcholine receptors

• Applicant: Dr. Jana Kusch
• Subject Area: Biophysics ; Biochemistry
• Term: from 2013 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 229708368

Nicotinic acetylcholine receptors are ligand-gated ion channels and belong to the cys-loop receptor family. They are expressed in both neuronal and non-neuronal cell types and play an important role in the transmission at cholinergic synapses. They are activated by the binding of acetylcholine to extracellular binding sites. Three distinct activation states are known: open, closed and desensitized. To shed light into the relation between ligand binding and receptor activation, these two processes will be studied simultaneously. To this end the confocal patch-clamp fluorometry will be applied, a method combining electrophysiological patch-clamp techniques and optical techniques using a fluorescently labelled ligand. The simultaneously recorded current and binding data will be used to discuss published models and to create alternative models describing the molecular gating behaviour. With this approach new insights into to activation gating of nicotinic acetylcholine receptors and related cys-loop receptors are expected. The detailed knowledge about the state-dependent binding and unbinding behaviour provide a base for a systematic development of agonists and antagonists for the pharmacological use.

• DFG Programme: Research Grants