Olgar 2017 MiP2017
Reactive oxygen species (ROS) and subsequent mitochondrial dysfunction prominently associated with onset of failing heart in senescent myocardium . Alterations of redox homeostasis lead to major cellular consequences such as matrix swelling, a release of apoptotic signaling molecules, and irreversible injury to the mitochondria. It also appears to be causally linked to the Ca2+ and Zn2+ handling in aging myocytes . However, the correlation between mitochondrial dysfunction and electrical and mechanical activity of the heart in aging individuals is still unclear. Therefore, we aimed to clarify whether impaired mitochondrial function contributes to electrical function of cardiomyocytes isolated from aged rat hearts.
Confocal florescence imaging examinations demonstrated that intracellular basal free levels of both Ca2+ ([Ca2+]i) and Zn2+ [Zn2+]i in cells from 24-month-old rats were about 5-fold higher than those of cells from 6-month-old rats. Furthermore, we measured markedly increased ROS levels in aging-heart cells as well as depolarized mitochondrial membrane potential (ΔΨmit). With electrophysiological measurement in cellular level, we measured depolarized resting membrane potential and markedly prolonged action potential (AP) duration. Our patch-clamp measurements demonstrated that the prolongation in AP are mostly due to alterations in K+-channel currents. Particularly, activated ATP-sensitive K+ channel currents (KATP) seem to act as a compansatory ionic-mechanism to protect the myocardium similar to ischemic damage . Our results exert that both repolarizing voltage gated K+ channels and KATP channel density reduced remarkably in senescent myocytes.
Taken together, our present data suggest that elevated ROS production and impaired mitochondrial function can account for increases in both [Ca2+]i and [Zn2+]i, which can in turn contribute to mechanical dysfunction of the heart. Moreover, the reduced voltage-dependent K+ channel currents and prolonged action potential in aging-cardiomyocytes are other contributing factors to abnormal heart function in aging-individuals.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration Pathology: Aging;senescence, Cardiovascular
Organism: Rat Tissue;cell: Heart
- Dept Biophysics, Faculty Med, Univ Ankara, Turkey. - firstname.lastname@example.org
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