박인경 (서울대학교)

한빛사논문

조회707

서울대학교

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Biosens. Bioelectron., Volume 200, 15 March 2022, 113903 | https://doi.org/10.1016/j.bios.2021.113903 Evaluation of site-selective drug effects on GABA receptors using nanovesicle-carbon nanotube hybrid devices

Inkyoung Park^a,1, Inwoo Yang^b,1, Youngtak Cho^a, Yoonji Choi^a, Junghyun Shin^a, Shashank Shekhar^a, Seung Hwan Lee^b,*, Seunghun Hong^a,*

^aDepartment of Physics and Astronomy, and the Institute of Applied Physics, Seoul National University, Seoul, 08826, Republic of Korea
^bDepartment of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, 15588, Republic of Korea

¹Inkyoung Park and Inwoo Yang contributed equally to this work.

^*Corresponding author

Abstract

Site-selective drug effects on the ion-channel activities of γ-aminobutyric acid type A (GABAA) receptors are evaluated by using a nanovesicle-carbon nanotube hybrid device. Here, nanovesicles containing GABAA receptors are immobilized on the channel region of a carbon nanotube field-effect transistor. The receptor responses of this hybrid device to GABA are detected with a high sensitivity down to ∼1 aM even in the presence of other neurotransmitters. Further, sensitivity differences between two GABAA-receptor-subunit compositions of α5β2γ2 and α1β2γ2 are assessed by normalizing the dose-dependent responses obtained from these hybrid devices. Specifically, the GABA concentration that produces 50% of maximal response (EC50) is obtained as ∼10 pM for α5β2γ2 subunits and ∼1 nM for α1β2γ2 subunits of GABAA receptor. Significantly, the potency profiles of both antagonist and agonist of GABAA receptor can be evaluated by analyzing EC50 values in the presence and absence of those drugs. A competitive antagonist increases the EC50 value of GABA by binding to the same site as GABA, while an allosteric agonist reduces it by binding to a different site. These results indicate that this hybrid device can be a powerful tool for the evaluation of candidate drug substances modulating GABA-mediated neurotransmission.

Keywords : Hybrid nanodevice, Carbon nanotube field-effect transistor, Nanovesicle, GABA receptor, Drug screening

논문정보

형식Research article
게재일2022년 03월 (BRIC 등록일 2022-02-10)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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