Abstract
Nanoscale electrical biosensors are promising tools for diagnostics and high-throughput screening systems. The electrical signal allows label-free assays with a high signal-to-noise ratio and fast real-time measurements. The challenge in developing such biosensors lies in functionally connecting a molecule detector to an electrical switch. Advances in this field have relied on synthetic ion-conducting pores and modified ion channels that are not yet suitable for biomolecule screening. Here we report the design and characterization of a novel bioelectric-sensing platform engineered by coupling an ion channel, which serves as the electrical probe, to G-protein-coupled receptors (GPCRs), a family of receptors that detect molecules outside the cell. These ion-channel-coupled receptors may potentially detect a wide range of ligands recognized by natural or altered GPCRs, which are known to be major pharmaceutical targets. This could form a unique platform for label-free drug screening.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biosensing Techniques / methods*
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Dopamine D2 Receptor Antagonists
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Drug Evaluation, Preclinical / methods
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Electric Conductivity
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Humans
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Ion Transport / drug effects
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Ligands
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Mice
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Multiprotein Complexes / genetics*
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Multiprotein Complexes / metabolism*
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying / genetics
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Potassium Channels, Inwardly Rectifying / metabolism
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Protein Engineering / methods*
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Receptor, Muscarinic M2 / agonists
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Receptor, Muscarinic M2 / antagonists & inhibitors
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Receptor, Muscarinic M2 / genetics*
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Receptor, Muscarinic M2 / metabolism*
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D2 / genetics*
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Receptors, Dopamine D2 / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
Substances
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Dopamine D2 Receptor Antagonists
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Kir6.2 channel
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Ligands
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Multiprotein Complexes
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptor, Muscarinic M2
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Receptors, Dopamine D2
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Recombinant Fusion Proteins