Rapid pacing of embryoid bodies impairs mitochondrial ATP synthesis by a calcium-dependent mechanism--a model of in vitro differentiated cardiomyocytes to study molecular effects of tachycardia.

Biochimica Et Biophysica Acta
Lorenz SchildU Lendeckel

Abstract

Tachycardia may cause substantial molecular and ultrastructural alterations in cardiac tissue. The underlying pathophysiology has not been fully explored. The purpose of this study was (I) to validate a three-dimensional in vitro pacing model, (II) to examine the effect of rapid pacing on mitochondrial function in intact cells, and (III) to evaluate the involvement of L-type-channel-mediated calcium influx in alterations of mitochondria in cardiomyocytes during rapid pacing. In vitro differentiated cardiomyocytes from P19 cells that formed embryoid bodies were paced for 24 h with 0.6 and 2.0 Hz. Pacing at 2.0 Hz increased mRNA expression and phosphorylation of ERK1/2 and caused cellular hypertrophy, indicated by increased protein/DNA ratio, and oxidative stress measured as loss of cellular thiols. Rapid pacing additionally provoked structural alterations of mitochondria. All these changes are known to occur in vivo during atrial fibrillation. The structural alterations of mitochondria were accompanied by limitation of ATP production as evidenced by decreased endogenous respiration in combination with decreased ATP levels in intact cells. Inhibition of calcium inward current with verapamil protected against hypertrophic response...Continue Reading

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Citations

Jan 15, 2016·Cardiovascular Research·Olurotimi O Mesubi, Mark E Anderson
Jan 20, 2016·Nature Communications·George EngGordana Vunjak-Novakovic
Feb 13, 2009·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Alicja BukowskaAndreas Goette
Mar 26, 2011·British Journal of Pharmacology·Mohammed M H Al-GayyarAzza B El-Remessy
Nov 27, 2010·Cardiovascular Therapeutics·Alicja BukowskaAndreas Goette
Dec 17, 2014·Biochimica Et Biophysica Acta·Carmen WolkeUwe Lendeckel
Oct 27, 2017·Circulation Journal : Official Journal of the Japanese Circulation Society·Masahide HaradaStanley Nattel
Jan 21, 2011·Physiological Reviews·Ulrich SchottenAndreas Goette
Dec 14, 2017·Herzschrittmachertherapie & Elektrophysiologie·Alicja BukowskaAndreas Goette
Jan 11, 2018·Herzschrittmachertherapie & Elektrophysiologie·Marc SühlingUwe Lendeckel
Apr 1, 2008·Experimental Biology and Medicine·Alicja BukowskaUwe Lendeckel
Mar 2, 2021·Experimental Biology and Medicine·Carmen WolkeUwe Lendeckel

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