Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.

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 physiolo...

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Autores principales:	Silmara R Sousa, Irina Vetter, Lotten Ragnarsson, Richard J Lewis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36a2bb1bfe22445e9da4655810a82158
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spelling	oai:doaj.org-article:36a2bb1bfe22445e9da4655810a821582021-11-18T07:52:09ZExpression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.1932-620310.1371/journal.pone.0059293https://doaj.org/article/36a2bb1bfe22445e9da4655810a821582013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23536870/?tool=EBIhttps://doaj.org/toc/1932-6203SH-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.Silmara R SousaIrina VetterLotten RagnarssonRichard J LewisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59293 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silmara R Sousa Irina Vetter Lotten Ragnarsson Richard J Lewis Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
description	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.
format	article
author	Silmara R Sousa Irina Vetter Lotten Ragnarsson Richard J Lewis
author_facet	Silmara R Sousa Irina Vetter Lotten Ragnarsson Richard J Lewis
author_sort	Silmara R Sousa
title	Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
title_short	Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
title_full	Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
title_fullStr	Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
title_full_unstemmed	Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.
title_sort	expression and pharmacology of endogenous cav channels in sh-sy5y human neuroblastoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/36a2bb1bfe22445e9da4655810a82158
work_keys_str_mv	AT silmararsousa expressionandpharmacologyofendogenouscavchannelsinshsy5yhumanneuroblastomacells AT irinavetter expressionandpharmacologyofendogenouscavchannelsinshsy5yhumanneuroblastomacells AT lottenragnarsson expressionandpharmacologyofendogenouscavchannelsinshsy5yhumanneuroblastomacells AT richardjlewis expressionandpharmacologyofendogenouscavchannelsinshsy5yhumanneuroblastomacells
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Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.

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