ArticleMolecular metabolism2021
CRISPR knockdown of Kcnq3 attenuates the M-current and increases excitability of NPY/AgRP neurons to alter energy balance.
Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The hypothalamus as a therapeutic target: Towards novel approaches for managing antipsychotic-induced weight gain.Reviews in endocrine & metabolic disorders · 2026Review
- Increased KCNQ3 expression in papillary thyroid cancer promotes proliferation and migration.Cancer cell international · 2025Article
- Early onset of hyperexcitability of medial mammillary body neurons in 5XFADJournal of neurophysiology · 2025Article
- Glutamatergic Input From Arcuate Nucleus Kiss1 Neurons to Preoptic Kiss1 Neurons Is Required for LH Surge in Female Mice.Endocrinology · 2025Article
- Intermittent fasting reprograms the brain proteome to prevent synaptic degeneration and cognitive impairment in vascular dementia.Theranostics · 2025Article
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- Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.bioRxiv : the preprint server for biology · 2024Article
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- Neuromodulator regulation and emotions: insights from the crosstalk of cell signaling.Frontiers in molecular neuroscience · 2024Review
- Heritability and recursive influence of host genetics on the rumen microbiota drive body weight variance in male Hu sheep lambs.Microbiome · 2023Article
- GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.PLoS biology · 2023Article
- The potassium channel auxiliary subunit Kvβ2 (Journal of neurophysiology · 2022Article
- Integrating genome-wide association studies and population genomics analysis reveals the genetic architecture of growth and backfat traits in pigs.Frontiers in genetics · 2022Article
- The PACAP Paradox: Dynamic and Surprisingly Pleiotropic Actions in the Central Regulation of Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Autism-associated mutations in KProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveArcuate nucleus neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons drive ingestive behavior. The M-current, a subthreshold non-inactivating potassium current, plays a critical role in regulating NPY/AgRP neuronal excitability. Fasting decreases while 17β-estradiol increases the M-current by regulating the mRNA expression of Kcnq2, 3, and 5 (Kv7.2, 3, and 5) channel subunits. Incorporating KCNQ3 into heteromeric channels has been considered essential to generate a robust M-current. Therefore, we investigated the behavioral and physiological effects of selective Kcnq3 deletion from NPY/AgRP neurons.
methodsWe used a single adeno-associated viral vector containing a recombinase-dependent Staphylococcus aureus Cas9 with a single-guide RNA to selectively delete Kcnq3 in NPY/AgRP neurons. Single-cell quantitative measurements of mRNA expression and whole-cell patch clamp experiments were conducted to validate the selective knockdown. Body weight, food intake, and locomotor activity were measured in male mice to assess disruptions in energy balance.
resultsThe virus reduced the expression of Kcnq3 mRNA without affecting Kcnq2 or Kcnq5. The M-current was attenuated, causing NPY/AgRP neurons to be more depolarized, exhibit a higher input resistance, and require less depolarizing current to fire action potentials, indicative of increased excitability. Although the resulting decrease in the M-current did not overtly alter ingestive behavior, it significantly reduced the locomotor activity as measured by open-field testing. Control mice on a high-fat diet exhibited an enhanced M-current and increased Kcnq2 and Kcnq3 expression, but the M-current remained significantly attenuated in KCNQ3 knockdown animals.
conclusionsThe M-current plays a critical role in modulating the intrinsic excitability of NPY/AgRP neurons that is essential for maintaining energy homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.