Pharmacological Blockade of High Threshold L-Type Calcium Channels in Cardiomyocytes Restores Respiratory Chain Activity Impaired by Vibration

Abstract

The transfer of calcium ions through the cell membrane of a cardiomyocyte is associated with overcoming a high energy barrier and can be impaired by vibration. Since drugs of the calcium channel blocker group are able to reduce damage to mitochondria and cell membranes, the effect of the calcium channel blocker nifedipine (adalat) at a dose of 7.5 mg/kg on the energy metabolism of cardiomyocytes in a vibration-mediated (56 sessions of vibration with a frequency of 44 Hz and an amplitude of 0.5 mm) model of cellular hypoxia was evaluated. The functional states of mitochondria in the composition of 30% homogenate of the myocardial tissue of the left ventricle of the rabbit heart were studied using the polarographic method with a closed galvanic oxygen sensor in a thermostatically controlled 1 mL cuvette with a protein content of 2.4 ± 0.5 mg, measured by a modified microbiuretic assay. In animals subjected to vibration in the presence of calcium channel blockers, the rate of endogenous respiration (V_e) remained at the level of intact animals and was 16.4 ± 4.1 [ng-atom O] min^–1 mg^–1 protein; sensitivity to amytal increased by 39% and sensitivity to malonate decreased by 40% compared with the indicators in animals subjected to vibration without pharmacological protection. The indicators of the ratio of the activity of mitochondrial enzyme complexes I and II and the processes of regulation in different metabolic states of mitochondria confirmed the restoration of the activity of mitochondrial enzyme complex I suppressed by vibration and the regulatory restriction of mitochondrial enzyme complex II. The revealed energy-protective effect of calcium channel blockers increased the vibration resistance of the tissue, preventing the development of necrotic changes in it.