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Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.
Wang, Yijie; Li, Qihao; Tao, Bo; Angelini, Marina; Ramadoss, Sivakumar; Sun, Baiming; Wang, Ping; Krokhaleva, Yuliya; Ma, Feiyang; Gu, Yiqian; Espinoza, Alejandro; Yamauchi, Ken; Pellegrini, Matteo; Novitch, Bennett; Olcese, Riccardo; Qu, Zhilin; Song, Zhen; Deb, Arjun.
Afiliación
  • Wang Y; Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Li Q; Cardiovascular Theme, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Tao B; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Angelini M; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Ramadoss S; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Sun B; California Nanosystems Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Wang P; Peng Cheng Laboratory, Shenzhen, Guangdong 518000, China.
  • Krokhaleva Y; Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Ma F; Cardiovascular Theme, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Gu Y; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Espinoza A; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Yamauchi K; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Pellegrini M; California Nanosystems Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Novitch B; Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Olcese R; Division of Cardiology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Qu Z; Cardiovascular Theme, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Song Z; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Deb A; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA.
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Cicatriz / Miocitos Cardíacos / Fibroblastos / Channelrhodopsins Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Cicatriz / Miocitos Cardíacos / Fibroblastos / Channelrhodopsins Límite: Animals Idioma: En Revista: Science Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos