Ion channels have been implicated in numerous neurological conditions, including epilepsy, migraines, and addiction. Existing therapies targeting these channels frequently result in undesirable side effects, highlighting the need for more precise and effective treatments. Neuronal nicotinic acetylcholine receptor (nAChR) is a key ion channel targeted for treating neurological and neuropsychiatric diseases. Notably, the α7 nAChR subtype has been implicated in schizophrenia and Alzheimer's disease. Within the central nervous system, α7 nAChRs primarily exhibit modulatory functions, distinct from other nAChRs that directly mediate neurotransmission. Resistance to Inhibitors of Cholinesterase (RIC-3), regulates the surface expression of functional nAChRs on neuronal membranes, which is altered in various diseases. For developing potent and efficacious drugs with reduced side effects, the intracellular domain (ICD) of α7 nAChR, particularly its protein-protein interaction with RIC-3, presents a promising therapeutic target.

We employed a pull-down assay using synthetic peptides of the α7 nAChR ICD to identify the segment mediating interaction with RIC-3. To investigate RIC-3's modulatory role in functional α7 nAChR expression, we injected corresponding cRNAs into Xenopus laevis oocytes and performed two-electrode voltage-clamp (TEVC) recordings. Current amplitudes were acquired and analyzed using a TEV-200 amplifier, a Digidata 1440A data interface, and pClamp 10.4 software.