Journal article
The α2δ subunit augments functional expression and modifies the pharmacology of CaV1.3 L-type channels
Cell calcium (Edinburgh), Vol.46(4), pp.282-292
10/2009
DOI: 10.1016/j.ceca.2009.08.006
PMID: 19796812
Abstract
The auxiliary Ca
V
α
2
δ-1 subunit is an important component of voltage-gated Ca2+ (CaV) channel complexes in many tissues and of great interest as a drug target. Nevertheless, its exact role in specific cell functions is still unknown. This is particularly important in the case of the neuronal L-type Ca
V
channels where these proteins play a key role in the secretion of neurotransmitters and hormones, gene expression, and the activation of other ion channels. Therefore, using a combined approach of patch clamp recordings and molecular biology, we studied the role of the Ca
V
α
2
δ-1 subunit on the functional expression and the pharmacology of recombinant L-type Ca
V
1.3 channels in HEK-293 cells. Co-expression of Ca
V
α
2
δ-1 significantly increased macroscopic currents and conferred the Ca
V
1.3α
1
/Ca
V
β
3
channels sensitivity to the antiepileptic/analgesic drugs gabapentin and AdGABA. In contrast, Ca
V
α
2
δ-1 subunits harboring point mutations in
N
-glycosylation consensus sequences or the proteolytic site as well as in conserved cysteines in the transmembrane δ domain of the protein, reduced functionality in terms of enhancement of Ca
V
1.3α
1
/Ca
V
β
3
currents. In addition, co-expression of the δ domain drastically inhibited macroscopic currents through recombinant Ca
V
1.3 channels possibly by affecting channel synthesis. Together these results provide several lines of evidence that the Ca
V
α
2
δ-1 auxiliary subunit may interact with Ca
V
1.3 channels and regulate their functional expression.
Details
- Title: Subtitle
- The α2δ subunit augments functional expression and modifies the pharmacology of CaV1.3 L-type channels
- Creators
- Arturo Andrade - Department of Physiology, Biophysics and Neuroscience; Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, MexicoAlejandro Sandoval - Department of Cell Biology; Cinvestav-IPN, Mexico City, MexicoRicardo González-Ramírez - Department of Cell Biology; Cinvestav-IPN, Mexico City, MexicoDiane Lipscombe - Department of Neuroscience, Brown University, Providence, RI, USAKevin P Campbell - Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USARicardo Felix - Department of Cell Biology; Cinvestav-IPN, Mexico City, Mexico
- Resource Type
- Journal article
- Publication Details
- Cell calcium (Edinburgh), Vol.46(4), pp.282-292
- DOI
- 10.1016/j.ceca.2009.08.006
- PMID
- 19796812
- NLM abbreviation
- Cell Calcium
- ISSN
- 0143-4160
- eISSN
- 1532-1991
- Grant note
- DOI: 10.13039/100007774, name: Instituto de Ciencia y Tecnología del Distrito Federal; DOI: 10.13039/501100003141, name: Consejo Nacional de Ciencia y Tecnología; DOI: 10.13039/501100003141, name: Consejo Nacional de Ciencia y Tecnología
- Language
- English
- Date published
- 10/2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020996202771
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