Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

48-POS Board 48 Structural and Functional Features of the ATP-dependent Potassium Channels in Mammalian Mitochondria Galina D. Mironova 1 , Evgeniy Y. Talanov 1 , Alexey A. Mosentsov 1 , Irina B. Krylova 2 , Vera V. Bulion 2 , Lubov L. Pavlik 1 . 1 Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region, Russian Federation, 2 Institute of Experimental Medicine, St. Petersburg, Russian Federation. By immunoelectron microscopy, in the rat liver and heart mitochondria, two channel proteins related to the ATP-dependent potassium ion transport system were identified. One of the proteins is immunoreactive to KIR and ROMR antibodies and is localized evenly over the mitochondria. The second protein, which has m. m. 57kD, is localized mainly around the periphery in rat heart mitochondria. The electrophysiological properties of the 57kDa channel protein were studied by its reconstruction into BLM. Low concentrations of ATP activate the channel, whereas high concentrations of ATP closed it. It was found that specific antibodies against this protein inhibit the ATP-dependent potassium transport in mitochondria, without any effect on other mitochondrial functions. MALDI protein analysis revealed that the 57kDa channel protein is 50% homologous to the precursor of calreticulin. Immunoblot analysis showed that the studied protein is practically absent in microsomes, where calreticulin is predominantly localized in microsomes. It was found that uridine diphosphate (UDP) is a metabolic activator of this channel. Using the experimental model of myocardial ischemia, it was observed that the intravenous’s injection of the precursor of UDP - uridine increases the concentration of UDP and UTP in the rat heart tissue, and causes pronounced anti-ischemic and anti-arrhythmic effects, manifested in a decrease in the necrosis zone, restoration of the heart rhythm, prevention of ATP and creatine phosphate decreases, as well as in the reduction of hydroperoxide in the myocardium of the experimental animals. The effect of uridine is eliminated by the selective inhibitor of the channel – 5-hydroxydecanoate. Uridine also acts as an antihypoxic factor in other models of oxidative stress. The work was supported by grants from the Government of RF (14.z50.31.0028), and partially from RNF (№ 16-15-00157), and RFBR (№ 16-04-00692а).

106