Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells

R. Luján, C. Aguado, F. Ciruela, X. Arus, A. Martín Belmonte, R. Alfaro Ruiz, J. Martinez Gomez, L. De La Ossa, M. Watanabe, J. Adelman, R. Shigemoto, Y. Fukazawa, Frontiers in Cellular Neuroscience 12 (2018).

Download
OA 6.83 MB

Journal Article | Published | English
Author
; ; ; ; ; ; ; ; ; ; ;
All
Department
Abstract
The small-conductance, Ca2+-activated K+ (SK) channel subtype SK2 regulates the spike rate and firing frequency, as well as Ca2+ transients in Purkinje cells (PCs). To understand the molecular basis by which SK2 channels mediate these functions, we analyzed the exact location and densities of SK2 channels along the neuronal surface of the mouse cerebellar PCs using SDS-digested freeze-fracture replica labeling (SDS-FRL) of high sensitivity combined with quantitative analyses. Immunogold particles for SK2 were observed on post- and pre-synaptic compartments showing both scattered and clustered distribution patterns. We found an axo-somato-dendritic gradient of the SK2 particle density increasing 12-fold from soma to dendritic spines. Using two different immunogold approaches, we also found that SK2 immunoparticles were frequently adjacent to, but never overlap with, the postsynaptic density of excitatory synapses in PC spines. Co-immunoprecipitation analysis demonstrated that SK2 channels form macromolecular complexes with two types of proteins that mobilize Ca2+: CaV2.1 channels and mGlu1α receptors in the cerebellum. Freeze-fracture replica double-labeling showed significant co-clustering of particles for SK2 with those for CaV2.1 channels and mGlu1α receptors. SK2 channels were also detected at presynaptic sites, mostly at the presynaptic active zone (AZ), where they are close to CaV2.1 channels, though they are not significantly co-clustered. These data demonstrate that SK2 channels located in different neuronal compartments can associate with distinct proteins mobilizing Ca2+, and suggest that the ultrastructural association of SK2 with CaV2.1 and mGlu1α provides the mechanism that ensures voltage (excitability) regulation by distinct intracellular Ca2+ transients in PCs.
Publishing Year
Date Published
2018-09-19
Journal Title
Frontiers in Cellular Neuroscience
Volume
12
Article Number
311
ISSN
IST-REx-ID

Cite this

Luján R, Aguado C, Ciruela F, et al. Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience. 2018;12. doi:10.3389/fncel.2018.00311
Luján, R., Aguado, C., Ciruela, F., Arus, X., Martín Belmonte, A., Alfaro Ruiz, R., … Fukazawa, Y. (2018). Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience, 12. https://doi.org/10.3389/fncel.2018.00311
Luján, Rafæl, Carolina Aguado, Francisco Ciruela, Xavier Arus, Alejandro Martín Belmonte, Rocío Alfaro Ruiz, Jesus Martinez Gomez, et al. “Sk2 Channels Associate with MGlu1α Receptors and CaV2.1 Channels in Purkinje Cells.” Frontiers in Cellular Neuroscience 12 (2018). https://doi.org/10.3389/fncel.2018.00311.
R. Luján et al., “Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells,” Frontiers in Cellular Neuroscience, vol. 12, 2018.
Luján R, Aguado C, Ciruela F, Arus X, Martín Belmonte A, Alfaro Ruiz R, Martinez Gomez J, De La Ossa L, Watanabe M, Adelman J, Shigemoto R, Fukazawa Y. 2018. Sk2 channels associate with mGlu1α receptors and CaV2.1 channels in Purkinje cells. Frontiers in Cellular Neuroscience. 12.
Luján, Rafæl, et al. “Sk2 Channels Associate with MGlu1α Receptors and CaV2.1 Channels in Purkinje Cells.” Frontiers in Cellular Neuroscience, vol. 12, 311, Frontiers Media, 2018, doi:10.3389/fncel.2018.00311.
All files available under the following license(s):
Creative Commons License:
CC-BYCreative Commons Attribution 4.0 International Public License (CC-BY 4.0)
Main File(s)
File Name
Access Level
OA Open Access
Last Uploaded
2018-12-17T08:49:03Z


Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar