G protein-gated inward rectifier potassium(GIRK)channels are widely distributed in the central nervous system and play important roles in maintaining the resting membrane potential of neurons,adjusting neuronal excitability,and regulating the release of neurotransmitter.Studies have shown that addictive behavior is closely related to the expression and activity of the GIRK channels in the brain reward system and the GIRK channels may be a potential target for addiction treatment.This article summarizes the recent research advances in GIRK channels in terms of structure,intracranial tissue distribution,and especially substance addiction.
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http://dx.doi.org/10.3881/j.issn.1000-503X.10972 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, NY 10065.
We examine the role of higher-order transient structures (HOTS) in M2R regulation of GIRK channels. Electron microscopic membrane protein location maps show that both proteins form HOTS that exhibit a statistical bias to be near each other. Theoretical calculations and electrophysiological measurements suggest that channel activity is isolated near larger M2R HOTS.
View Article and Find Full Text PDFElife
December 2024
Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, United States.
Hypothalamic kisspeptin (Kiss1) neurons are vital for pubertal development and reproduction. Arcuate nucleus Kiss1 (Kiss1) neurons are responsible for the pulsatile release of gonadotropin-releasing hormone (GnRH). In females, the behavior of Kiss1 neurons, expressing Kiss1, neurokinin B (NKB), and dynorphin (Dyn), varies throughout the ovarian cycle.
View Article and Find Full Text PDFNeuropharmacology
March 2025
Department of Neurology, Columbia University Irving Medical Center, 710 West 168th Street, New York, NY, 10032-3784, USA. Electronic address:
Tumor associated epilepsy is a common and debilitating co-morbidity of brain tumors, for which inadequate treatments are available. Additionally, animal models suggest a potential link between seizures and tumor progression. Our group has previously described a mouse model of diffusely infiltrating glioma and associated chronic epilepsy.
View Article and Find Full Text PDFJ Recept Signal Transduct Res
August 2024
Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA.
Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.
View Article and Find Full Text PDFNeurochem Res
November 2024
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, 420111, Russia.
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