G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels: Molecular, cellular, and subcellular diversity
G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels are mainly expressed in excitable cells such as neurons and atrial myocytes, where they can respond to a wide variety of neurotransmitters. Four GIRK subunits have been found in mammals (GIRK1-4) and act as downstream targets for various Ga...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/42854 |
| Acceso en línea: | https://www.hh.um.es/Abstracts/Vol_/_/__18822.htm https://hdl.handle.net/10578/42854 |
| Access Level: | acceso abierto |
| Palabra clave: | G protein-coupled receptors (GPCRs) GIRK channels Hyperpolarization Immunoelectron microscopy Immunohistochemistry Inhibition Macromolecular complexes Neurological diseases Neurons Pathology Pharmacological targets Potassium efflux Subcellular localization |
| Sumario: | G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels are mainly expressed in excitable cells such as neurons and atrial myocytes, where they can respond to a wide variety of neurotransmitters. Four GIRK subunits have been found in mammals (GIRK1-4) and act as downstream targets for various Gai/o-linked G protein-coupled receptors (GPCRs). Activation of GIRK channels produces a postsynaptic efflux of potassium from the cell, responsible for hyperpolarization/inhibition of the neuron. A growing body of evidence suggests that dysregulation of GIRK signalling can lead to excessive or deficient neuronal excitability, which contributes to neurological diseases and disorders. Therefore, GIRK channels are proposed as new pharmacological targets. The function of GIRK channels in neurons is not only determined by their biophysical properties but also by their cellular and subcellular localization patterns and densities on the neuronal surface. GIRK channels can be located within several subcellular compartments, where they have many different functional implications. This subcellular localization changes dynamically along the neuronal surface in response to drug intake. Ongoing research is focusing on determining the proteins that form macromolecular complexes with GIRK channels and are responsible for fast and precise signalling under physiological conditions, and how their alteration is implicated in pathological conditions. In this review, the distinct regional, cellular, and subcellular distribution of GIRK channel subunits in the brain will be discussed in view of their possible functional and pathological implications. |
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