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http://purl.uniprot.org/citations/21622683http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21622683http://www.w3.org/2000/01/rdf-schema#comment"

Aims

Previous studies suggested that T-type Ca(2+)-current (I(CaT))-blockers improve cardiac remodelling, but all available I(CaT)-blockers have non-specific actions on other currents and/or functions. To clarify the role of I(CaT) in cardiac remodelling, we studied mice with either of the principal cardiac I(CaT)-subunits (Cav3.1 or Cav3.2) knocked out.

Methods and results

Adult male Cav3.1- or Cav3.2-knockout (Cav3.1(-/-), Cav3.2(-/-)) mice and respective wild-type (WT) littermate controls were subjected to left anterior descending coronary artery ligation to create myocardial infarction (MI). Echocardiography and programmed electrical stimulation were performed at baseline and 4 weeks post-MI. At baseline, Cav3.1(-/-) mice had slowed heart rates and longer PR intervals vs. WT, but no other electrophysiological and no haemodynamic differences. Cav3.2(-/-) showed no differences vs. WT. Contractile indices (left ventricular fractional shortening and ejection fraction) decreased more post-MI in Cav3.1(-/-) mice than in Cav3.1(+/+) (e.g. by 34 and 29% for WT; 50 and 45% for Cav3.1(-/-), respectively; P < 0.05 for each). Cav3.1(-/-) mice had increased ventricular tachycardia (VT) inducibility post-MI (9 of 11, 82%) vs. WT (3 of 10, 30%; P < 0.05). Cav3.2(-/-) mice were not different in cardiac function or VT inducibility vs. WT. Quantitative polymerase chain reaction showed that Cav3.1 is the major I(CaT)-subunit and that no compensatory Cav3.2 up-regulation occurs in Cav3.1(-/-) mice. Cav3.1(-/-) and Cav3.2(-/-) mice had no mRNA expression for the knocked-out gene, at baseline or post-MI.

Conclusion

Our findings suggest that, contrary to suggestions from previous studies with (imperfectly selective) pharmacological agents having T-type Ca(2+)-channel-blocking actions, elimination of Cav3.1 expression leads to impaired cardiac function and enhanced arrhythmia vulnerability post-MI, whereas Cav3.2 elimination has no effect."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.org/dc/terms/identifier"doi:10.1093/cvr/cvr082"xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Shi Y.F."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Levesque P.C."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Tardif J.C."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Dobrev D."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Nattel S."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Charpentier F."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Duval F."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Gillis M.A."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Le Quang K."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Qi X.Y."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Naud P."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/author"Comtois P."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/pages"420-428"xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/title"Role of T-type calcium channel subunits in post-myocardial infarction remodelling probed with genetically engineered mice."xsd:string
http://purl.uniprot.org/citations/21622683http://purl.uniprot.org/core/volume"91"xsd:string
http://purl.uniprot.org/citations/21622683http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21622683
http://purl.uniprot.org/citations/21622683http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21622683
http://purl.uniprot.org/uniprot/#_E0CYZ3-mappedCitation-21622683http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21622683
http://purl.uniprot.org/uniprot/#_E9Q6E4-mappedCitation-21622683http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21622683