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

L Pacini, S Suffredini, D Ponti, R Coppini… - Canadian Journal of …, 2013 - cdnsciencepub.com
L Pacini, S Suffredini, D Ponti, R Coppini, G Frati, G Ragona, E Cerbai, A Calogero
Canadian Journal of Physiology and Pharmacology, 2013cdnsciencepub.com
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 …
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 Ca2+-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.
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