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cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes

1997Journal article Open access
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dc.contributor.authorVerde, Ignacio
dc.contributor.authorRivet-Bastide, Michèlept
dc.contributor.authorVandecasteele, Grégoire
dc.contributor.authorHatem, Stéphanept
dc.contributor.authorBénardeau, Agnèspt
dc.contributor.authorMercadier, Jean-Jacquespt
dc.contributor.authorFischmeister, Rodolphept
dc.date.accessioned2010-04-28T10:06:47Z
dc.date.available2010-04-28T10:06:47Z
dc.date.issued1997
dc.description.abstractEHNA (Erythro-9-[2-hydroxy-3-nonyl]adenine) is a wellknown inhibitor of adenosine deaminase. Recently, EHNA was shown to block the activity of purified soluble cGMPstimulated phosphodiesterase (PDE2) from frog, human, and porcine heart with an apparent Ki value of approximately 1 microM and with negligible effects on Ca2+/calmodulin PDE (PDE1), cGMP-inhibited PDE (PDE3), and low Km cAMP-specific PDE (PDE4) (Méry, P.F., C. Pavoine, F. Pecker, and R. Fischmeister. 1995. Mol. Pharmacol. 48:121-130; Podzuweit, T., P. Nennstiel, and A. Muller. 1995. Cell. Signalling. 7:733- 738). To investigate the role of PDE2 in the regulation of cardiac L-type Ca2+ current (ICa), we have examined the effect of EHNA on ICa in freshly isolated human atrial myocytes. Extracellular application of 0.1-10 microM EHNA induced an increase in the amplitude of basal ICa ( approximately 80% at 1 microM) without modification of the current-voltage or inactivation curves. The maximal stimulatory effect of EHNA on ICa was comparable in amplitude with the maximal effect of isoprenaline (1 microM), and the two effects were not additive. The effect of EHNA was not a result of adenosine deaminase inhibition, since 2'-deoxycoformycin (1-30 microM), another adenosine deaminase inhibitor with no effect on PDE2, or adenosine (1-10 microM) did not increase ICa. In the absence of intracellular GTP, the substrate of guanylyl cyclase, EHNA did not increase ICa. However, under similar conditions, intracellular perfusion with 0.5 microM cGMP produced an 80% increase in ICa. As opposed to human cardiomyocytes, EHNA (1-10 microM) did not modify ICa in isolated rat ventricular and atrial myocytes. We conclude that basal ICa is controlled by PDE2 activity in human atrial myocytes. Both PDE2 and PDE3 may contribute to keep the cyclic nucleotides concentrations at minimum in the absence of adenylyl and/or guanylyl cyclase stimulation.
dc.identifier.urihttp://hdl.handle.net/10400.6/549
dc.language.isoengpt
dc.titlecGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytespt
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue99:2710-8pt
oaire.citation.titleJournal of Clinical Investigationpt
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.rightsopenAccesspt
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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