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Article

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

1
Synaptic Structure Laboratory, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02008 Albacete, Spain
2
Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas, ISCIII, 28049 Madrid, Spain
3
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editors: Antonio Ferrer-Montiel and Antonio Felipe
Int. J. Mol. Sci. 2021, 22(20), 11106; https://doi.org/10.3390/ijms222011106
Received: 23 September 2021 / Revised: 11 October 2021 / Accepted: 12 October 2021 / Published: 14 October 2021
(This article belongs to the Special Issue Membrane Channels in Physiology and Pathology)
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´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. View Full-Text
Keywords: Alzheimer´s disease; hippocampus; GIRK channels; immunohistochemistry; electron microscopy; histoblot; P301S; APP/PS1; AD mouse model Alzheimer´s disease; hippocampus; GIRK channels; immunohistochemistry; electron microscopy; histoblot; P301S; APP/PS1; AD mouse model
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MDPI and ACS Style

Alfaro-Ruiz, R.; Martín-Belmonte, A.; Aguado, C.; Hernández, F.; Moreno-Martínez, A.E.; Ávila, J.; Luján, R. 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. Int. J. Mol. Sci. 2021, 22, 11106. https://doi.org/10.3390/ijms222011106

AMA Style

Alfaro-Ruiz R, Martín-Belmonte A, Aguado C, Hernández F, Moreno-Martínez AE, Ávila J, Luján R. 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. International Journal of Molecular Sciences. 2021; 22(20):11106. https://doi.org/10.3390/ijms222011106

Chicago/Turabian Style

Alfaro-Ruiz, Rocío, Alejandro Martín-Belmonte, Carolina Aguado, Félix Hernández, Ana E. Moreno-Martínez, Jesús Ávila, and Rafael Luján. 2021. "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" International Journal of Molecular Sciences 22, no. 20: 11106. https://doi.org/10.3390/ijms222011106

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