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This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (RTI2018-095812-B-I00) to R.L., and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229) to R.L.

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Hernandez Perez, FelixAuthor

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November 15, 2021
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The Expression and Localisation of G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels Is Differentially Altered in the Hippocampus of Two Mouse Models of Alzheimer's Disease

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 22 (20): 11106- - 2021-10-01 22(20), DOI: 10.3390/ijms222011106

Authors: Alfaro-Ruiz, Rocio; Martin-Belmonte, Alejandro; Aguado, Carolina; Hernandez, Felix; Moreno-Martinez, Ana Esther; Avila, Jesus; Lujan, Rafael;

Affiliations

ISCIII, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28049, Spain - Author
UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain - Author
Univ Castilla La Mancha, Fac Med, Inst Invest Discapacidades Neurol IDINE, Synapt Struct Lab,Dept Ciencias Med, Campus Biosanitario,C Almansa 14, Albacete 02008, Spain - Author

Abstract

G protein-gated inwardly rectifying K+ (GIRK) channels are the main targets controlling excitability and synaptic plasticity on hippocampal neurons. Consequently, dysfunction of GIRK-mediated signalling has been implicated in the pathophysiology of Alzheimer & PRIME;s disease (AD). Here, we provide a quantitative description on the expression and localisation patterns of GIRK2 in two transgenic mice models of AD (P301S and APP/PS1 mice), combining histoblots and immunoelectron microscopic approaches. The histoblot technique revealed differences in the expression of GIRK2 in the two transgenic mice models. The expression of GIRK2 was significantly reduced in the hippocampus of P301S mice in a laminar-specific manner at 10 months of age but was unaltered in APP/PS1 mice at 12 months compared to age-matched wild type mice. Ultrastructural approaches using the pre-embedding immunogold technique, demonstrated that the subcellular localisation of GIRK2 was significantly reduced along the neuronal surface of CA1 pyramidal cells, but increased in its frequency at cytoplasmic sites, in both P301S and APP/PS1 mice. We also found a decrease in plasma membrane GIRK2 channels in axon terminals contacting dendritic spines of CA1 pyramidal cells in P301S and APP/PS1 mice. These data demonstrate for the first time a redistribution of GIRK channels from the plasma membrane to intracellular sites in different compartments of CA1 pyramidal cells. Altogether, the pre- and post-synaptic reduction of GIRK2 channels suggest that GIRK-mediated alteration of the excitability in pyramidal cells could contribute to the cognitive dysfunctions as described in the two AD animal models.

Keywords

ad mouse modelalzheimer´s diseaseapp/ps1electron microscopygirk channelshippocampushistoblotp301s<p>app/ps1</p>ActivationAd mouse modelAlzheimer ' s diseaseAlzheimer diseaseAlzheimer´s diseaseAmyloid-betaAnimalsApp/ps1BrainCa1 region, hippocampalCell membraneCnsDendritesDisease models, animalDiversityElectron microscopyG protein-coupled inwardly-rectifying potassium channelsGaba(b) receptorsGirk channelsHippocampusHistoblotImmunohistochemistryK+ channelsKcnj6 protein, mouseMaleMapt protein, humanMessenger-rnasMice, transgenicNeuronal plasticityP301sPresenilin-1Psen1 protein, humanTauTau proteins

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 69/297, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.8, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-04, the following number of citations:

  • WoS: 10
  • Scopus: 13
  • Europe PMC: 12

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 31.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 31 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.25.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/704453