Is VDAC2 a new target for the treatment of cardiac pathologies? (literature review)

Abstract

The most modern approach to solve the problems of treating cardiac arrhythmias is to influence the intracellular mechanisms of regulation of calcium homeostasis in the cell. VDAC2 (voltage-dependent anion channel 2) are channels in the outer mitochondrial membrane, which, as the latest studies have shown, perform a specific function in the heart, participating in the regulation of calcium homeostasis. VDAC2 provide mitochondrial and SR (sarcoplasmic reticulum) tethering, interact with RyR2, and are a channel through which calcium ions pass into the intermembrane space. The article analyzes the role of VDAC2 in the normal functioning of the heart, discusses the mechanism by which, by acting on VDAC2, it is possible to reduce the concentration of calcium ions in the cytosol in order to eliminate calcium sparks. Thus, promising is the direction of synthesis or identification of molecules that, by binding to VDAC2, would transfer it to a state of low conductivity, that is, to one in which it is more permeable to calcium ions. Data are presented on the promising effects of efsevin, a substance capable of eliminating heart rhythm disturbances due to a decrease in the concentration of calcium ions in the cytoplasm. In addition, possible undesirable consequences caused by a large influx of calcium ions into mitochondria are presented, including inhibition of pyruvate dehydrogenase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase, permeabilization of the outer and inner mitochondrial membranes, and, as a result, cell death.

Keywords

• vdac2
• calcium homeostasis
• efsevin
• calcium ions
• mitochondrial membranes