Nanovesicle-carbon nanotube hybrid device for the evaluation of site-selective drug effects on GABA receptors

We report a nanovesicle-carbon nanotube hybrid device for the evaluation of drug effects on ion-channel activities of γ-aminobutyric acid type A (GABA_A) receptors. Here, carbon nanotube field-effect transistor (CNT-FET) devices were fabricated via microfabrication processes, and nanovesicles containing GABA_A receptors were immobilized on the channel region of CNT-FET. This device allowed us to selectively detect GABA responses with a high sensitivity down to 1 aM. Further, we could discriminate well-known sensitivity differences between two GABA_A-receptor-subunit compositions of α5β2γ2 and α1β2γ2 by normalizing the dose-dependent responses of the hybrid devices. Significantly, we could evaluate the potency profiles of both antagonist and agonist of GABA_A receptors by analyzing the GABA concentration that produces 50% of maximal response (EC₅₀) in the presence and absence of those drugs. An allosteric agonist reduces the EC₅₀ value by binding to a different site, while a competitive antagonist increases it by binding to the same site as GABA. These results show that this hybrid device can be a powerful tool for the evaluation of various antipsychotic drug candidates binding to GABA_A receptors.