Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

106

48-POS

Board 48

Structural and Functional Features of the ATP-dependent Potassium Channels in

Mammalian Mitochondria

Galina D. Mironova

, Evgeniy Y. Talanov

, Alexey A. Mosentsov

, Irina B. Krylova

, Vera V.

Bulion

, Lubov L. Pavlik

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences,

Pushchino, Moscow region, Russian Federation,

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).