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Automated Patch Clamp Recordings of GPCR-Gated Ion Channels: Targeting the MC4-R/Kir7.1 Potassium Channel Complex

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Potassium Channels

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2796))

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Abstract

Automated patch clamp recording is a valuable technique in drug discovery and the study of ion channels. It allows for the precise measurement and manipulation of channel currents, providing insights into their function and modulation by drugs or other compounds. The melanocortin 4 receptor (MC4-R) is a G protein-coupled receptor (GPCR) crucial to appetite regulation, energy balance, and body weight. MC4-R signaling is complex and involves interactions with other receptors and neuropeptides in the appetite-regulating circuitry. MC4-Rs, like other GPCRs, are known to modulate ion channels such as Kir7.1, an inward rectifier potassium channel, in response to ligand binding. This modulation is critical for controlling ion flow across the cell membrane, which can influence membrane potential, excitability, and neurotransmission. The MC4-R is the target for the anti-obesity drug Imcivree. However, this drug is known to lack optimal potency and also has side effects. Using high-throughput techniques for studying the MC4-R/Kir7.1 complex allows researchers to rapidly screen many compounds or conditions, aiding the development of drugs that target this system. Additionally, automated patch clamp recording of this receptor–channel complex and its ligands can provide valuable functional and pharmacological insights supporting the development of novel therapeutic strategies. This approach can be generalized to other GPCR-gated ion channel functional complexes, potentially accelerating the pace of research in different fields with the promise to uncover previously unknown aspects of receptor–ion channel interactions.

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Acknowledgments

We thank the Center for Chemical Genomics at the University of Michigan Life Sciences Institute for the collaboration and for providing the compounds from the Drug Repurposing Library. This work was partly funded by the Michigan Drug Discovery Initiative Grant No. U076275-22204S (to C. C. Hernandez and L. E. Gimenez), the Klatskin-Sutker Discovery Fund Award No. G026085 (to C. C. Hernandez), and NIH grant 1S10OD025203 to the Center for Chemical Genomics at the University of Michigan.

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Authors and Affiliations

  1. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA

    Ciria C. Hernandez, Luis E. Gimenez & Roger D. Cone

  2. Center for Chemical Genomics, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA

    Ciria C. Hernandez

  3. Department of Molecular and Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, MI, USA

    Roger D. Cone

Authors
  1. Ciria C. Hernandez
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  2. Luis E. Gimenez
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  3. Roger D. Cone
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Correspondence to Ciria C. Hernandez .

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Editors and Affiliations

  1. Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi”, University of Bologna, Cesena, Italy

    Simone Furini

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Hernandez, C.C., Gimenez, L.E., Cone, R.D. (2024). Automated Patch Clamp Recordings of GPCR-Gated Ion Channels: Targeting the MC4-R/Kir7.1 Potassium Channel Complex. In: Furini, S. (eds) Potassium Channels. Methods in Molecular Biology, vol 2796. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3818-7_14

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  • DOI: https://doi.org/10.1007/978-1-0716-3818-7_14

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  • Publisher Name: Humana, New York, NY

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