MITOCHONDRIAL REACTIVE OXYGEN SPECIES (ROS) PRODUCTION CAUSES STRETCH-INDUCED INCREASE IN CALCIUM SPARKRATE

K. Kaihara, K. Naruse

Cardiovascular Physiology, Okayama University, Okayama, Japan

Abstract

Introduction: We have previously reported that myocardial stretch induces an increase in Ca2+ spark rate. In the present study, we investigated the involvement of mitochondrial reactive oxygen species (ROS) production in stretch-induced acute increase in Ca2+ spark rate.
Methods: Isolated mouse ventricular myocytes were exposed to 5-8 % axial stretch using carbon fibers attached to both cell ends. Diastolic spark rate was studied using Fluo-4 loaded cells. ROS production was studied using DCF loaded cells. The slope of the DCF signal indicates ROS production.
Results: Axial stretch significantly increased Ca2+ spark rate (142.1 ▒ 13.1 %, n = 10), and slope of DCF signal (107.7 ▒ 3.2 %, n = 14). Applying 5 ÁM of FCCP (mitochondrial uncoupler) in the presence of 5 ÁM oligomycin (to prevent ATP depletion) blunted the increase in both spark rate (98.8 ▒ 4.5%, n = 11) and slope of DCF (99.2 ▒ 1.7%, n = 10).
Conclusions: Our present results suggest that stretch-induced mitochondrial ROS production possibly play a role in stretch-induced increase in Ca2+ spark rate.