Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons

Title:
Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons
Authors:
Shapiro, Mark S.; Gomeza, Jesus; Hamilton, Susan E.; Hille, Bertil; Loose, Michael D.; Nathanson, Neil M.; Roche, John P.; Wess, Jürgen
Abstract:
Many different G protein-coupled receptors modulate the activity of Ca2+ and K+ channels in a variety of neuronal types. There are five known subtypes (M1–M5) of muscarinic acetylcholine receptors. Knockout mice lacking the M1, M2, or M4 subtypes are studied to determine which receptors mediate modulation of voltage-gated Ca2+ channels in mouse sympathetic neurons. In these cells, muscarinic agonists modulate N- and L-type Ca2+ channels and the M-type K+ channel through two distinct, G-protein mediated pathways. The fast and voltage-dependent pathway is lacking in the M2 receptor knockout mice. The slow and voltage-independent pathway is absent in the M1 receptor knockout mice. Neither pathway is affected in the M4 receptor knockout mice. Muscarinic modulation of the M current is absent in the M1 receptor knockout mice, and can be reconstituted in a heterologous expression system using cloned channels and M1 receptors. Our results using knockout mice are compared with pharmacological data in the rat.
Citation:
Shapiro, Mark S., Jesus Gomeza, Susan E. Hamilton, et al. 2001. "Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons." Life Sciences 68(22-23): 2481-2487.
Publisher:
Elsevier
DATE ISSUED:
2001-04
Department:
Neuroscience
Type:
Article
PUBLISHED VERSION:
10.1016/S0024-3205(01)01042-6
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0024320501010426
PERMANENT LINK:
http://hdl.handle.net/11282/606587

Full metadata record

DC FieldValue Language
dc.contributor.authorShapiro, Mark S.en
dc.contributor.authorGomeza, Jesusen
dc.contributor.authorHamilton, Susan E.en
dc.contributor.authorHille, Bertilen
dc.contributor.authorLoose, Michael D.en
dc.contributor.authorNathanson, Neil M.en
dc.contributor.authorRoche, John P.en
dc.contributor.authorWess, Jürgenen
dc.date.accessioned2016-04-22T13:00:11Zen
dc.date.available2016-04-22T13:00:11Zen
dc.date.issued2001-04en
dc.identifier.citationShapiro, Mark S., Jesus Gomeza, Susan E. Hamilton, et al. 2001. "Identification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neurons." Life Sciences 68(22-23): 2481-2487.en
dc.identifier.issn0024-3205en
dc.identifier.urihttp://hdl.handle.net/11282/606587en
dc.description.abstractMany different G protein-coupled receptors modulate the activity of Ca2+ and K+ channels in a variety of neuronal types. There are five known subtypes (M1–M5) of muscarinic acetylcholine receptors. Knockout mice lacking the M1, M2, or M4 subtypes are studied to determine which receptors mediate modulation of voltage-gated Ca2+ channels in mouse sympathetic neurons. In these cells, muscarinic agonists modulate N- and L-type Ca2+ channels and the M-type K+ channel through two distinct, G-protein mediated pathways. The fast and voltage-dependent pathway is lacking in the M2 receptor knockout mice. The slow and voltage-independent pathway is absent in the M1 receptor knockout mice. Neither pathway is affected in the M4 receptor knockout mice. Muscarinic modulation of the M current is absent in the M1 receptor knockout mice, and can be reconstituted in a heterologous expression system using cloned channels and M1 receptors. Our results using knockout mice are compared with pharmacological data in the rat.en
dc.language.isoen_USen
dc.publisherElsevieren
dc.identifier.doi10.1016/S0024-3205(01)01042-6en
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0024320501010426en
dc.subject.departmentNeuroscienceen_US
dc.titleIdentification of subtypes of muscarinic receptors that regulate Ca2+ and K+ channel activity in sympathetic neuronsen_US
dc.typeArticleen
dc.identifier.journalLife Sciencesen
dc.subject.keywordMuscarinic receptoren_US
dc.subject.keywordG proteinen_US
dc.subject.keywordCa2+ channelen_US
dc.subject.keywordM currenten_US
dc.identifier.volume68en_US
dc.identifier.issue22-23en_US
dc.identifier.startpage2481en_US
dc.rightsArchived with thanks to Life Sciencesen
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