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J Neurosci. 2014 Oct 29;34(44):14793-802. doi: 10.1523/JNEUROSCI.2038-14.2014.

Coassembly and coupling of SK2 channels and mGlu5 receptors.

Author information

1
Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina.
2
Laboratori de Neurobiologia, Institut d'Investigacions Biomèdiques de Bellvitge, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Spain.
3
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-0818, Japan.
4
Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.
5
Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, and.
6
Instituto de Investigación en Discapacidades Neurológicas, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, 02008 Albacete, Spain Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.
7
Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, Rafael.Lujan@uclm.es adelman@ohsu.edu fciruela@ub.edu.

Abstract

Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca(2+) wave-dependent activation of small-conductance Ca(2+)-activated K(+) (SK) channels. Here, we show that mGlu5 receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu5 receptor stimulation activated apamin-sensitive SK2-mediated K(+) currents. In addition, coexpression of mGlu5 receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu5 receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu5 receptors and SK2 channels that reflects their molecular coassembly.

KEYWORDS:

SK2 channel; apamin; electron microscopy; mGlu5 receptor; oligomerization

PMID:
25355231
PMCID:
PMC6608419
DOI:
10.1523/JNEUROSCI.2038-14.2014
[Indexed for MEDLINE]
Free PMC Article

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