Cytoskeletal disarray increases arrhythmogenic vulnerability during sympathetic stimulation in a model of hypertrophic cardiomyopathy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 07 2023
12 07 2023
Historique:
received:
12
04
2023
accepted:
06
07
2023
medline:
14
7
2023
pubmed:
13
7
2023
entrez:
12
7
2023
Statut:
epublish
Résumé
Familial hypertrophic cardiomyopathy (FHC) patients are advised to avoid strenuous exercise due to increased risk of arrhythmias. Mice expressing the human FHC-causing mutation R403Q in the myosin heavy chain gene (MYH6) recapitulate the human phenotype, including cytoskeletal disarray and increased arrhythmia susceptibility. Following in vivo administration of isoproterenol, mutant mice exhibited tachyarrhythmias, poor recovery and fatigue. Arrhythmias were attenuated with the β-blocker atenolol and protein kinase A inhibitor PKI. Mutant cardiac myocytes had significantly prolonged action potentials and triggered automaticity due to reduced repolarization reserve and connexin 43 expression. Isoproterenol shortened cycle length, and escalated electrical instability. Surprisingly isoproterenol did not increase Ca
Identifiants
pubmed: 37438479
doi: 10.1038/s41598-023-38296-2
pii: 10.1038/s41598-023-38296-2
pmc: PMC10338442
doi:
Substances chimiques
Isoproterenol
L628TT009W
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11296Subventions
Organisme : NIA NIH HHS
ID : R01 AG063796
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL086350
Pays : United States
Organisme : NIH HHS
ID : T32 HL086350
Pays : United States
Informations de copyright
© 2023. The Author(s).
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