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Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes

1999Journal article Open access
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dc.contributor.authorVerde, Ignacio
dc.contributor.authorVandecasteele, Grégoire
dc.contributor.authorLezoualc'h, Frank
dc.contributor.authorFischmeister, Rodolphe
dc.date.accessioned2010-04-28T10:06:48Z
dc.date.available2010-04-28T10:06:48Z
dc.date.issued1999
dc.description.abstractPhosphorylation of cardiac L-type Ca2+ channels by cyclic AMP-dependent protein kinase (PKA) plays a determinant role in the hormonal regulation of myocardial contraction. PKA increases the mean open probability of individual Ca2+ channels which results in an increase in the macroscopic L-type calcium current (ICa) (McDonald et al., 1994). Activation of PKA usually results from an increased production of cyclic AMP by activation of membrane receptors positively coupled to adenylyl cyclase via stimulatory G proteins (Gs). The best documented of such a regulation is the positive inotropic effect of sympathomimetic amines, such as isoprenaline (Hartzell et al., 1991; Hove-Madsen et al., 1996). However, cardiac myocytes, as most other cell types, also possess a negative feedback mechanism to adenylyl cyclase activation which is constituted of the cyclic nucleotide phosphodiesterases (PDEs), a family of enzymes that break down cyclic AMP into 5'-AMP (Beavo, 1995). Cyclic nucleotide PDE activity, at any given location within the cell, will counterbalance the synthesis of cyclic AMP and determine the extent of PKA activation and, hence, of protein phosphorylation. In particular, at the sarcolemmal membrane, this balance between adenylyl cyclase and PDE activities will control the degree of ICa stimulation upon hormonal activation (Fischmeister & Hartzell, 1991; Hove-Madsen et al., 1996). Other factors are involved, such as cyclic AMP compartmentation (Jurevicius & Fischmeister, 1996), PKA tethering to the membrane (Gao et al., 1997), or phosphatase activity (Wiechen et al., 1995). [...]
dc.identifier.urihttp://hdl.handle.net/10400.6/551
dc.languageeng
dc.titleCharacterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytespt
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue127:65-74pt
oaire.citation.titleBritish Journal of Pharmacologypt
person.familyNameVerde
person.familyNameVandecasteele
person.givenNameIgnacio
person.givenNameGrégoire
person.identifier.ciencia-idD012-1D7C-791A
person.identifier.orcid0000-0003-3492-5725
person.identifier.orcid0000-0002-4046-4171
person.identifier.ridM-3991-2013
person.identifier.scopus-author-id55913729400
rcaap.rightsopenAccess
rcaap.typearticlept
relation.isAuthorOfPublicationbfb58284-b817-4267-9628-8fa150aa681c
relation.isAuthorOfPublicationd11a75df-74f0-4cb6-a49a-0ee646ffc342
relation.isAuthorOfPublication.latestForDiscoverybfb58284-b817-4267-9628-8fa150aa681c

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