Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease
Open accessAbstract
G protein-gated inwardly rectifying potassium (GIRK) channels hyperpolarize neurons in response to activation of many different G protein-coupled receptors and thus control the excitability of neurons through GIRK-mediated self-inhibition, slow synaptic potentials and volume transmission. GIRK channel function and trafficking are highly dependent on the channel subunit composition. Pharmacological investigations of GIRK channels and studies in animal models suggest that GIRK activity has an important role in physiological responses, including pain perception and memory modulation. Moreover, abnormal GIRK function has been implicated in altering neuronal excitability and cell death, which may be important in the pathophysiology of diseases such as epilepsy, Down's syndrome, Parkinson's disease and drug addiction. GIRK channels may therefore prove to be a valuable new therapeutic target.
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Several types of K+ channels function as general gatekeepers of neuronal excitability in numerous experimental systems.
“there is increasing evidence that several types of K+ channels function as general gatekeepers of neuronal excitability in numerous experimental systems79, 80”
From Neurobiology of resilience (2012) · cites this paper as [79]
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Bidirectional Influence of Limbic GIRK Channel Activation on Innate Avoidance Behavior
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Kahanovitch, U., Tsemakhovich, V., Berlin, S., Rubinstein, M., Styr, B., Castel, R., Peleg, S., Tabak, G., Dessauer, C. W., Ivanina, T., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.283218 · Cited by 29 · see citing works
Xu, Y., Cantwell, L., Molosh, A. I., Plant, L. D., Gazgalis, D., Fitz, S. D., Dustrude, E. T., Yang, Y., Kawano, T., Garai, S., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011527 · Cited by 32 · see citing works
Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels
Nguyen, H., Glaaser, I. W., & Slesinger, P. A. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1386645 · Cited by 29 · see citing works
Self-citationKozek, K. A., Du, Y., Sharma, S., Prael, F. J., Spitznagel, B. D., Kharade, S. V., Denton, J. S., Hopkins, C. R., & Weaver, C. D. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00287 · Cited by 26 · see citing works
Direct modulation of TRPC ion channels by Gα proteins
Kang, H., Kim, J., Park, C. H., Jeong, B., & So, I. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1362987 · Cited by 14 · see citing works
Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery
Tanaka, M. (2026) · Biomedicines · doi:10.3390/biomedicines14061265
- Authors
- Lüscher, C., & Slesinger, P. A.
- Affiliations
- University of Geneva (CH)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Lüscher, Christian
- Slesinger, Paul A.
- Venue
- Nature Reviews Neuroscience
- Published
- 2010-04-14
- Volume
- 11
- Issue
- 5
- Pages
- 301-315
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC3052907
- OpenAlex
- W2138098510
- Cited by
- 617
- References
- 184
- Citations by year
- 2026: 32 · 2025: 35 · 2024: 29 · 2023: 43 · 2022: 40 · 2021: 39 · 2020: 41 · 2019: 36 · 2018: 42 · 2017: 46 · 2016: 38 · 2015: 42 · 2014: 50 · 2013: 41 · 2012: 33
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- McKnight Endowment Fund for Neuroscience
- National Institute on Drug Abuse (R01DA019022)
- National Institute of Neurological Disorders and Stroke (R01NS037682, R01 NS37682)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- GIRK channels, G protein-coupled inwardly rectifying potassium channels, neuronal excitability, G protein-coupled receptors, channel subunit composition, epilepsy, Down syndrome, drug addiction, Parkinson's disease, pain perception, memory modulation, neuronal cell death, therapeutic target
- MeSH terms
- Animals, Brain, Brain Diseases, Models, Neurological, Neurons, Pain, G Protein-Coupled Inwardly-Rectifying Potassium Channels
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