Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.
Science
; 381(6665): 1480-1487, 2023 09 29.
Article
en En
| MEDLINE
| ID: mdl-37769108
ABSTRACT
After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
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Cicatriz
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Miocitos Cardíacos
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Fibroblastos
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Channelrhodopsins
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos