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

Abstract

The transport of calcium ions across the cardiomyocyte cellular membrane is associated with crossing a high energy barrier and can be dysregulated by the vibration. Calcium channel blockers are a group of medication that reduce damage of mitochondria and cell membranes. In this study, the effects of nifedipine (adalat), a calcium channel blocker drug, 7.5 mg/kg on energy metabolism of cardiomyocytes which underwent vibration induced hypoxia (exposure to 56 vibration sessions at a single frequency, 44 Hz with an amplitude of 0.5 mm) were evaluated. The functional states of mitochondria in 30% rabbit left ventricular myocardial tissue homogenate were studied polarographically using a closed galvanic oxygen sensor in a 1 ml cuvette with thermostatic holder, the protein concentration in the system was 2.4 ± 0.5 mg and a modified microbiuret method was used for protein determination. In animals injected with calcium channel blockers and exposed to vibration, the rate of endogenous respiration (V e) remained at the level as in intact animals and was 16.4 ± 4.1 [ng-atom O] min–1mg–1 protein, amytal sensitivity increased by 39%, and malonate sensitivity decreased by 40% as compared to animals that were not injected with calcium channel blockers but exposed to vibration. The indices of the ratio of the activity of mitochondrial enzyme complex I and complex II and the processes of regulation of mitochondria in different metabolic states indicate that the activity of mitochondrial complex I , inhibited by vibration, is restored and mitochondrial complex II exhibits limited regulatory functions. This study has shown the energy-protective action of calcium channel blockers, due to which tissue resistance in response to vibration increases, thereby preventing the development of necrotic changes in the tissue.