Disruption of potassium homeostasis within cells is one of the key moments in the emergence of pathogenic seizures in epilepsy. It is known that this disease is characterized by a decrease in the membrane potential of the cell and an increase in the extracellular concentration of potassium ions. By increasing the level of extracellular potassium ions, from 2 to 9 mM, cell membrane potential decreases from -63 mV to -52 mV, and depolarization leads to the appearance of seizures. The mechanism of occurrence of epileptic seizures is not yet clear. The task of investigating the energy and ion exchange in the tissues in epilepsy is very important.
The research used three groups of animals: 1 - rat Krushinsky Molodkina (KM), which is highly susceptible to convulsive seizures in response to sound; 2 - KM rats that 2 days before the experiment were subjected to acoustic stress; 3 - control rats, which are not prone to audiogenic epilepsy. These animals were studied in order to examine the following parameters, which are important for the function of rat brain and liver mitochondria: respiratory rate and intensity of oxidative phosphorylation, the rate of transport of K+ ions, potassium and Ca2+ capacity, and the concentration of malonic dialdehyde.
Respiration velocity of rat brain mitochondria from KM was 20-25% less than control. No significant changes in energy metabolism in KM rats compared to control were observed. Changes when using substrates - glutamate / malate (during the first portion of the respiratory chain) in brain mitochondria were found. Consequently, changes in rat brain mitochondrial respiration were observed only in KM during the 2nd and 3rd regions of the respiratory chain, and only in KM exposed to acoustic stress prior to measurements. In liver mitochondria, these changes were observed on both substrates involved in respiration in KM rats both without sound action as well as KM rats exposed to acoustic stress.
Speed of potassium ion uptake in the mitochondria of both brain and liver of all KM rat groups also decreased compared with control animals (average 20-30%), while the amount of potassium in them is reduced slightly. Concentration of malonic dialdehyde was higher in brain and liver mitochondria of KM rats exposed to acoustic stress than KM rats and control. Amount of accumulated calcium, defined as mitochondrial Ca2+ capacity, is reduced in mitochondria from the brain and liver of KM rats after acoustic stress, which means an increase in the chance of discovery of a Ca2+-dependent cyclosprorin A (CsA)-sensitive pore within these animals, whereas changes in function of palmitate-induced lipid pores in these animals were not observed.
This work was supported by grants from the Government of the Russian Federation № 14.Z50.31.0028 and DPNNiT № 2014/281/2495.