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

IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology

Biophysics Pub Date : 2024-09-27 DOI:10.1134/S0006350924700301

V. V. Vorobieva, O. S. Levchenkova, P. D. Shabanov

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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.

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药理阻断心肌细胞中的高阈值 L 型钙通道可恢复受振动影响的呼吸链活动

钙离子通过心肌细胞膜的转移与克服高能量屏障有关，并会受到振动的影响。由于钙通道阻滞剂类药物能够减少对线粒体和细胞膜的损伤，因此我们评估了剂量为 7.5 毫克/千克的钙通道阻滞剂硝苯地平（adalat）在振动介导的细胞缺氧模型（振动 56 次，频率为 44 赫兹，振幅为 0.5 毫米）中对心肌细胞能量代谢的影响。采用极谱法研究了兔子左心室心肌组织 30% 匀浆成分中线粒体的功能状态，在恒温控制的 1 毫升比色皿中装有封闭式电化学氧传感器，蛋白质含量为 2.4 ± 0.5 毫克，通过改良的微生物测定法进行测量。在钙通道阻滞剂作用下受到振动的动物，其内源性呼吸速率（Ve）保持在完整动物的水平，为 16.4 ± 4.1 [ng-atom O] min-1 mg-1 蛋白质；与未受药物保护的动物的指标相比，对氨甲蝶呤的敏感性增加了 39%，对丙二酸盐的敏感性降低了 40%。线粒体酶复合物 I 和 II 的活性比率指标以及线粒体不同代谢状态下的调节过程证实，受振动抑制的线粒体酶复合物 I 的活性得到恢复，线粒体酶复合物 II 的调节受到限制。所揭示的钙通道阻滞剂的能量保护作用增强了组织的抗振性，防止了组织坏死性变化的发展。

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来源期刊

Biophysics Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

1.20

自引率

0.00%

发文量

期刊介绍： Biophysics is a multidisciplinary international peer reviewed journal that covers a wide scope of problems related to the main physical mechanisms of processes taking place at different organization levels in biosystems. It includes structure and dynamics of macromolecules, cells and tissues; the influence of environment; energy transformation and transfer; thermodynamics; biological motility; population dynamics and cell differentiation modeling; biomechanics and tissue rheology; nonlinear phenomena, mathematical and cybernetics modeling of complex systems; and computational biology. The journal publishes short communications devoted and review articles.