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Identification of chloride channel from cardiac tissue mitochondria

Biophysics

2024

Mgr. Zuzana Ševčíková Tomášková, PhD.

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Faculty of Mathematics, Physics, and Informatics, Comenius University in Bratislava

Chloride channels are involved in the regulation of mitochondrial membrane potential under both physiological and pathological conditions. During ischemia/reperfusion injury, the chloride channels contribute to the generation of post-ischemic arrhythmias. Chloride channels from cardiac mitochondria are well described at the electrophysiological level. It was confirmed that the so-called CLIC (chloride intracellular channel) proteins are located in the mitochondria of cardiac cells. Under certain conditions, these proteins can function as ion channels. Furthermore, a ligand of translocator protein, which is also localized in mitochondria, has the same antiarrhythmic effects as a chloride channel inhibitor. The aim of the work is to link this knowledge and find out whether the native chloride channels that we described in our laboratory are identical to any of the CLIC isoforms and whether these proteins are in close contact with the translocator protein, which would explain the observed antiarrhythmic effect. The obtained results should clarify the molecular identity of native chloride channels from cardiac mitochondria and also explain the regulation of the chloride channel by ligands of the translocator protein. Methods: confocal microscopy (FRET analysis, induction of oxidative stress by laser, analysis of mitochondrial networks), molecular electrophysiology (measurement of current through one ion channel), selected methods of molecular biology, work with tissues and cell cultures.