Expression and pharmacology of endogenous Ca-v channels in SH-SY5Y human neuroblastoma cells

Sousa, Silmara R., Vetter, Irina, Ragnarsson, Lotten and Lewis, Richard J. (2013) Expression and pharmacology of endogenous Ca-v channels in SH-SY5Y human neuroblastoma cells. PloS One, 8 3: . doi:10.1371/journal.pone.0059293

Author Sousa, Silmara R.
Vetter, Irina
Ragnarsson, Lotten
Lewis, Richard J.
Title Expression and pharmacology of endogenous Ca-v channels in SH-SY5Y human neuroblastoma cells
Formatted title
Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-03-25
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0059293
Open Access Status DOI
Volume 8
Issue 3
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These cells are derived from human sympathetic neuronal tissue and thus, express a number of the Cav channel subtypes essential for regulation of important physiological functions, such as heart contraction and nociception, including the clinically validated pain target Cav2.2. We have detected mRNA transcripts for a range of endogenous expressed subtypes Cav1.3, Cav2.2 (including two Cav1.3, and three Cav2.2 splice variant isoforms) and Cav3.1 in SH-SY5Y cells; as well as Cav auxiliary subunits α2δ1–3, β1, β3, β4, γ1, γ4–5, and γ7. Both high- and low-voltage activated Cav channels generated calcium signals in SH-SY5Y cells. Pharmacological characterisation using ω-conotoxins CVID and MVIIA revealed significantly (~ 10-fold) higher affinity at human versus rat Cav2.2, while GVIA, which interacts with Cav2.2 through a distinct pharmacophore had similar affinity for both species. CVID, GVIA and MVIIA affinity was higher for SH-SY5Y membranes vs whole cells in the binding assays and functional assays, suggesting auxiliary subunits expressed endogenously in native systems can strongly influence Cav2.2 channels pharmacology. These results may have implications for strategies used to identify therapeutic leads at Cav2.2 channels.
Keyword Neuronal calcium-channel
Recombinant N-type
Gated ion channels
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e59293

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 26 May 2013, 01:28:07 EST by System User on behalf of Institute for Molecular Bioscience