Abstract
We investigated how oxidative stress (OS) alters Ca2+ handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of N-acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca2+ transients (SCaTs), diastolic Ca2+ sparks (CaS) and Ca2+ waves (CaW), recorded by confocal techniques, and L-type Ca2+ current (ICa), assessed by whole-cell patch clamp, were evaluated in MetS and Control cells. MetS myocytes exhibited decreased SCaTs and CaS frequency but unaffected CaW propagation. In Control cells, NAC/DTT reduced RyR2/SERCA2a activity blunting SCaTs, CaS frequency and CaW propagation, suggesting that basal ROS optimised Ca2+ signalling by maintaining RyR2/SERCA2a function and that these proteins facilitate CaW propagation. Conversely, NAC/DTT in MetS recovered RyR2/SERCA2a function, improving SCaTs and CaS frequency, but unexpectedly decreasing CaW propagation. We hypothesised that OS decreases RyR2/SERCA2a activity at early MetS, and while decreased SERCA2a favours CaW propagation, diminished RyR2 restrains it.
Acknowledgements
The authors thank Rodolfo Fernández, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional, Ciudad de México, for excellent technical assistance. The authors thank Yolanda Contreras Vargas, Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, for reference editing.
Disclosure statement
The authors declare no conflict of interest.
Data availability statement
The authors confirm that the data supporting the findings of this study are available within the article [and/or] its Supplementary materials. Further details may be available on request from the corresponding author (KC)