Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice.

Luca Pacini, Silvia Suffredini, Donatella Ponti, Raffaele Coppini, Giacomo Frati, Giuseppe Ragona, Elisabetta Cerbai, Antonella Calogero

Research output: Contribution to journalArticle

Abstract

Early growth response-1 one gene (Egr-1), one of the immediate early response genes, plays an important role in the adaptive response of the myocardium to hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on cardiac function. Egr-1 knock-out (Egr-1(-/-)) homozygous mice were employed to evaluate the electrophysiological and molecular properties of left ventricular cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium measurements, real-time PCR, and Western blot. Action potential was prolonged and diastolic potential was positive-shifted in VCMs isolated from Egr-1(-/-) mice, in comparison with those from their wild-type (WT) littermates. The calcium content of the sarcoplasmic reticulum was reduced and the decay time for steady-state calcium transient slowed down. Serca2, Ryr, L-type Ca(2+)-channel, and PLB mRNA expression were reduced in Egr-1(-/-) mice compared with the controls. Moreover, Serca2 protein was reduced, while the amount of Ncx1 protein was increased in Egr-1(-/-) hearts compared with those of the WT littermates. Furthermore, genes involved in heart development (GATA-4, TGF-β) and in Egr-1 regulation (Nab1, Nab2) were down regulated in Egr-1(-/-) mice. These results suggest that Egr-1 plays a pivotal role in regulating excitation-contraction coupling in cardiac myocytes.

Original languageEnglish
Pages (from-to)1135-1142
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume91
Issue number12
Publication statusPublished - Dec 2013

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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  • Cite this

    Pacini, L., Suffredini, S., Ponti, D., Coppini, R., Frati, G., Ragona, G., Cerbai, E., & Calogero, A. (2013). Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice. Canadian Journal of Physiology and Pharmacology, 91(12), 1135-1142.