Pathways modulating neural KCNQ/M (Kv7) potassium channels
Abstract
K(+) channels play a crucial role in regulating the excitability of neurons. Many K(+) channels are, in turn, regulated by neurotransmitters. One of the first neurotransmitter-regulated channels to be identified, some 25 years ago, was the M channel. This was categorized as such because its activity was inhibited through stimulation of muscarinic acetylcholine receptors. M channels are now known to be composed of subunits of the Kv7 (KCNQ) K(+) channel family. However, until recently, the link between the receptors and the channels has remained elusive. Here, we summarize recent developments that have begun to clarify this link and discuss their implications for physiology and medicine.
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KCNQ channels are maintained in the open state by PI(4,5)P2; M1 receptor activation via Gαq/PLCβ1 causes a robust decrease in PI(4,5)P2 and channel closure; IP3 and DAG do not directly contribute; PI(4,5)P2 resynthesis reopens the channels.
“The best characterised example is the KCNQ channels which are maintained in the open state allowing K+ to move freely (Figure 6B). Upon stimulation with the muscarinic agonist, M1 receptors are activated which couple to Gαq and activate PLCβ1. A robust decrease in PI(4,5)P2 causes channel closure; the PI(4,5)P2 hydrolysis products IP3 and DAG do not contribute directly to channel regulation. Res”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [115]
High levels of cAMP might potentiate these actions through PKA modulation of Kv7 channels, producing coordinated cAMP shunting of network inputs.
“High levels of cAMP might potentiate these actions through PKA modulation of Kv7 channels95, thus producing a coordinated cAMP shunting of network inputs.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [95]
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- Authors
- Delmas, P., & Brown, D. A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University College London (GB)
- Venue
- Nature Reviews Neuroscience
- Published
- 2005-11-01
- Volume
- 6
- Issue
- 11
- Pages
- 850-862
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2079373480
- Cited by
- 686
- References
- 2
- Citations by year
- 2026: 23 · 2025: 22 · 2024: 29 · 2023: 27 · 2022: 31 · 2021: 32 · 2020: 44 · 2019: 25 · 2018: 32 · 2017: 34 · 2016: 25 · 2015: 35 · 2014: 34 · 2013: 44 · 2012: 35
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- 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 › Nicotinic Acetylcholine Receptors Study
- Keywords
- Kv7 potassium channels, KCNQ channels, M-channels, muscarinic receptors, neuronal excitability, receptor-channel coupling, G protein signaling
- MeSH terms
- Animals, Humans, Neurons, Receptors, Muscarinic, Second Messenger Systems, Ion Channel Gating, Up-Regulation, Phosphatidylinositol 4,5-Diphosphate
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