Department of Microbiology and Physiological Systems
Amino Acids, Peptides, and Proteins | Cell Biology | Cells | Neuroscience and Neurobiology
OBJECTIVES: We examined whether two G protein-coupled receptors (GPCRs), muscarinic M1 receptors (M1Rs) and dopaminergic D2 receptors (D2Rs), utilize endogenously released fatty acid to inhibit L-type Ca(2+) channels, CaV1.3. HEK-293 cells, stably transfected with M1Rs, were used to transiently transfect D2Rs and CaV1.3b with different CaVbeta-subunits, allowing for whole-cell current measurement from a pure channel population.
RESULTS: M1R activation with Oxotremorine-M inhibited currents from CaV1.3b coexpressed with alpha2delta-1 and a beta1b, beta2a, beta3, or beta4-subunit. Surprisingly, the magnitude of inhibition was less with beta2a than with other CaVbeta-subunits. Normalizing currents revealed kinetic changes after modulation with beta1b, beta3, or beta4, but not beta2a-containing channels. We then examined if D2Rs modulate CaV1.3b when expressed with different CaVbeta-subunits. Stimulation with quinpirole produced little inhibition or kinetic changes for CaV1.3b coexpressed with beta2a or beta3. However, quinpirole inhibited N-type Ca(2+) currents in a concentration-dependent manner, indicating functional expression of D2Rs. N-current inhibition by quinpirole was voltage-dependent and independent of phospholipase A2 (PLA2), whereas a PLA2 antagonist abolished M1R-mediated N-current inhibition. These findings highlight the specific regulation of Ca(2+) channels by different GPCRs. Moreover, tissue-specific and/or cellular localization of CaV1.3b with different CaVbeta-subunits could fine tune the response of Ca(2+) influx following GPCR activation.
Acetylcholine, CaVβ subunit, Dopamine, L-type calcium current
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Copyright © The Author(s) 2018. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
BMC Res Notes. 2018 Sep 27;11(1):681. doi: 10.1186/s13104-018-3783-x. Link to article on publisher's site
BMC research notes
Roberts-Crowley ML, Rittenhouse AR. (2018). Modulation of CaV1.3b L-type calcium channels by M1 muscarinic receptors varies with CaVbeta subunit expression. Open Access Articles. https://doi.org/10.1186/s13104-018-3783-x. Retrieved from https://escholarship.umassmed.edu/oapubs/3611
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.