ROS Dependent Modulation of Calcium Sparks in Cardiomyocytes
Mitochondrial regulation of cytosolic calcium ([Ca2+]i) is thought to depend on the mitochondrial inner membrane potential (ΔΨm). ΔΨm arises from activity of the electron transport chain and is thought to play a critical role in all ion movements across the inner membrane. With ΔΨmito ≈ −150 mV to −200 mV, there is clearly a strong electrochemical potential for the movement of Ca2+ from the cytosol (about 100 nM) into the matrix (around 100 nM). If significant rapid Ca2+ influx occurs, then ΔΨmito per se should influence the time-course, frequency, magnitude and other characteristics of Ca2+ sparks and the [Ca2+]i transients. Tetramethylrhodamine methyl ester (TMRM) was used to monitor ΔΨmito in freshly isolated rat cardiomyocytes and photon stress was used to depolarize the mitochondria. In addition to the changes in electrochemical potential for Ca2+ entry, depolarization of mitochondria was associated with an increase in cellular reactive oxygen species (ROS) as measured by DCF (as has been previously reported by several laboratories). Quantitative analysis of these findings permits us to separate the influence of each on the changes in Ca2+ signaling observed. Consistent with findings by Zhou et al., 2011, we report a role for local [ROS] in altering Ca2+ signaling.ReferencesZhou, L., Aon., M.A., Lui, T., O'Rourke, B. Dynamic modulation of Ca2+ sparks by mitochondrial oscillations in isolated guinea pig cardiomyocytes under oxidative stress. JMCC. 2011. 51(5):632–9.