CaMKII and eIF4E participate in arrhythmias generation during aging.

HARNICHAR EZEQUIEL; SANTALLA MANUELA; VALVERDE CARLOS; MATTIAZZI ALICIA; FERRERO PAOLA

Buenos Aires

Congreso; Congreso: Señalización celular y expresión génica; 2013

SAIB

We use Drosophila melanogaster for studying cardiac diseases. One transgenic strain containing a fluorescent reporter system that senses intracellular twitch Ca2+ transient increases was utilized. We observed changes in the frequency of Ca2+ transients with age in semi-intac fly heart preparations and its putative modification by 1) The inhibition of Ca2+-calmodulin-dependent protein kinase (CaMKII), involved in Ca2+ cycling and 2) the reduction in eIF4E expression, an eukaryotic translation initiation factor. Results: Flies between 60 and 70 days old showed reduction of heart rate compared with 7 days old flies and widespred distribution of cardiac periods (intervals between transient increases of Ca2+). Arrhythmicity index (standard deviation of the heart period), increased from 0.27 to 0.52 (n=12). CaMKII inhibition reduced dispersion of cardiac periods distribution and arrhythmicity index from 0.27 to 0.19 (n = 21). Lower levels of eIF4E reduced dispersion of cardiac periods distribution and arrhythmicity index from 0.27 to 0.09 in 7 days old (n=18) flies. The results indicate that CaMKII regulates cardiac function in Drosophila and is an arrhythmogenic molecule. More important, eIF4E participates in the genesis of arrhythmias independently of its canonical function as translation factor, pointing to this factor as a putative new candidate involved in the pathophysiology of the mammalian heart.