Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct;239(2):e13981.
doi: 10.1111/apha.13981. Epub 2023 May 14.

Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

Sara Landi  1 , Federica Giannetti  1 , Patrizia Benzoni  1 , Giulia Campostrini  1 , Giuliana Rossi  2 , Chiara Piantoni  1 , Giorgia Bertoli  1 , Chiara Bonfanti  2 , Luca Carnevali  1 , Annalisa Bucchi  1 , Mirko Baruscotti  1 , Giorgia Careccia  2 , Graziella Messina  2 , Andrea Barbuti  1
Affiliations
Free article

Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

Sara Landi et al. Acta Physiol (Oxf). 2023 Oct.
Free article

Abstract

Aims: Nfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members (Nfia, b, c, x). Nfix plays important roles in the development and function of several organs. In muscle development, Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow-twitching fibres. Nfix is expressed also in the heart, but its function has been never investigated before. We studied Nfix role in this organ.

Methods: Using Nfix-null and wild type (WT) mice we analyzed: (1) the expression pattern of Nfix during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis.

Results and conclusions: Nfix expression start in the heart from E12.5. Adult hearts of Nfix-null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix-null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix-null mice express a significantly larger L-type calcium current (Cacna1d + Cacna1c). Interestingly, downregulation of Nfix by sh-RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in ICaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L-type calcium current, modulates heart rate.

Keywords: L-type calcium current; Nfix; ion channels; neonatal rat ventricular cardiomyocytes; sinus node; tachycardia.

PubMed Disclaimer

Comment in

References

REFERENCES

    1. Piper M, Gronostajski R, Messina G. Nuclear factor one X in development and disease. Trends Cell Biol. 2019;29(1):20-30.
    1. Messina G, Biressi S, Monteverde S, et al. Nfix regulates fetal-specific transcription in developing skeletal muscle. Cell. 2010;140(4):554-566.
    1. Rossi G, Antonini S, Bonfanti C, et al. Nfix regulates temporal progression of muscle regeneration through modulation of myostatin expression. Cell Rep. 2016;14(9):2238-2249.
    1. Chaudhry AZ, Lyons GE, Gronostajski RM. Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development. Dev Dyn. 1997;208(3):313-325.
    1. Barbuti A, Robinson RB. Stem cell-derived nodal-like cardiomyocytes as a novel pharmacologic tool: insights from sinoatrial node development and function. Pharmacol Rev. 2015;67(2):368-388.