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Trends Neurosci. 2014 Jan;37(1):20-9. doi: 10.1016/j.tins.2013.10.006. Epub 2013 Nov 21.

New insights into the therapeutic potential of Girk channels.

Author information

1
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. Electronic address: Rafael.Lujan@uclm.es.
2
Department of Pharmacology, University of Minnesota, 321 Church Street South East, Minneapolis, MN 55455, USA.
3
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.
4
Department of Pharmacology, University of Minnesota, 321 Church Street South East, Minneapolis, MN 55455, USA. Electronic address: wickm002@umn.edu.

Abstract

G protein-dependent signaling pathways control the activity of excitable cells of the nervous system and heart, and are the targets of neurotransmitters, clinically relevant drugs, and drugs of abuse. G protein-gated inwardly rectifying potassium (K(+)) (Girk/Kir3) channels are a key effector in inhibitory signaling pathways. Girk-dependent signaling contributes to nociception and analgesia, reward-related behavior, mood, cognition, and heart-rate regulation, and has been linked to epilepsy, Down syndrome, addiction, and arrhythmias. We discuss recent advances in our understanding of Girk channel structure, organization in signaling complexes, and plasticity, as well as progress on the development of subunit-selective Girk modulators. These findings offer new hope for the selective manipulation of Girk channels to treat a variety of debilitating afflictions.

PMID:
24268819
PMCID:
PMC3880623
DOI:
10.1016/j.tins.2013.10.006
[Indexed for MEDLINE]
Free PMC Article

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