Peroxynitrite-Induced Intracellular Ca2+ Depression in Cardiac Myocytes: Role of Sarco/Endoplasmic Reticulum Ca2+...

Area of Science:

• Cardiovascular Physiology
• Biochemistry
• Cellular Biology

Background:

• Peroxynitrite (ONOO-), a reactive nitrogen species, is elevated in cardiovascular diseases and negatively impacts myocardial function.
• Proteins regulating cardiac calcium (Ca2+) homeostasis are potential targets of ONOO--induced damage.

Purpose of the Study:

• To investigate the mechanisms by which ONOO- affects intracellular Ca2+ ([Ca2+]i) regulation in cardiac myocytes.
• To examine the impact of ONOO- on Ca2+ handling proteins, including the ryanodine receptor (RyR).

Main Methods:

• Isolated rat myocytes were treated with 3-morpholinosydnonimine N-ethylcarbamide (SIN-1), an ONOO- donor.
• Intracellular Ca2+ transients, contractions, and caffeine-evoked Ca2+ release were measured.
• Phosphorylation levels of RyR2 at the Ser-2814 site were assessed.

Main Results:

• SIN-1 dose-dependently decreased Ca2+ transient amplitude and contraction, and prolonged Ca2+ transient decay.
• ONOO--induced effects were mitigated by the ONOO- decomposition catalyst FeTMPyP.
• Impaired sarcoplasmic reticulum Ca2+ uptake and increased RyR2-mediated Ca2+ release were observed, along with reduced RyR2 phosphorylation at Ser-2814.

Conclusions:

• ONOO- disrupts cardiac myocyte Ca2+ handling through impaired sarcoplasmic reticulum Ca2+-ATPase activity and enhanced RyR2 Ca2+ release.
• These ONOO--induced alterations in Ca2+ homeostasis may contribute to cardiac dysfunction in conditions like diabetes, nephropathy, and hypertension.