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Abstract <p>Muscle atrophy and decreased strength are observed under hypokinesia; a decrease in strength can occur at the earliest stages of functional unloading. To study the relationship between calcium-dependent processes in the fiber and changes in the contractile properties of <i>m. soleus</i>, a 3-day unloading was used in male Wistar rats that were injected with nifedipine, a dihydropyridine receptor (DHPR) blocker, or ouabain, a cardiac glycoside that binds to the α-subunit of Na<sup>+</sup>,K<sup>+</sup>-ATP-ase. In two series of experiments, 3 groups of rats were used (16 animals in each group): control (C), hindlimb suspension (3HS), and either hindlimb suspension + nifedipine (3HS + N) or hindlimb suspension + ouabain (3HS + Ou). It was found that functional unloading resulted in a decrease in the mass of <i>m. soleus</i> in all groups with functional unloading (3HS, 3HS + N, and 3HS + Ou) (<i>p</i> &lt; 0.05). After 3-day hindlimb suspension without drugs, the cross-sectional area (CSA) of fast and slow muscle fibers (MF) decreased, the level of Ca<sup>2+</sup> in the MF myoplasm increased, and the maximum strength of single and tetanic contractions of <i>m. soleus</i> decreased relative to the control (<i>p</i> &lt; 0.05). Inhibition of DHPR during 3-day-long functional unloading prevented a decrease in CSA, a decrease in strength, an increase in the level of Ca<sup>2+</sup> in the myoplasm of MF, and a decrease in the maximum strength of single and tetanic contraction of <i>m. soleus</i>. Upon the addition of ouabain, an increase in CSA and a decrease in the level of Ca<sup>2+</sup> in the myoplasm were observed, while the specific (normalized by the physiological cross-section of the muscle) maximum force of single and tetanic contraction of <i>m. soleus</i> in animals decreased significantly compared to the group without drugs (3HS). However, ouabain significantly affected the passive mechanical properties of <i>m. soleus</i>, namely, the maximum peak force and maximum force at the end of the stretching test in muscles with the administration of the drug did not differ from the intact control group. Thus, the use of ouabain and nifedipine leads to the prevention of the accumulation of myoplasmic calcium under the functional unloading, which is accompanied by the preservation of specific stiffness and muscle strength, slowing the decrease in the cross-sectional area of MF and preventing a change in the percentage of MF towards fast-type fibers.</p>

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The Effect of Na+,K+-ATPase and Dihydropyridine Receptor Activity on Ca2+ Content and Contractile Properties of m. soleus in Rats under Three-Day Functional Unloading

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • T. L. Nemirovskaya,
  • K. A. Sharlo,
  • S. A. Tyganov,
  • D. A. Sidorenko,
  • R. O. Bokov,
  • K. A. Zaripova

摘要

Abstract

Muscle atrophy and decreased strength are observed under hypokinesia; a decrease in strength can occur at the earliest stages of functional unloading. To study the relationship between calcium-dependent processes in the fiber and changes in the contractile properties of m. soleus, a 3-day unloading was used in male Wistar rats that were injected with nifedipine, a dihydropyridine receptor (DHPR) blocker, or ouabain, a cardiac glycoside that binds to the α-subunit of Na+,K+-ATP-ase. In two series of experiments, 3 groups of rats were used (16 animals in each group): control (C), hindlimb suspension (3HS), and either hindlimb suspension + nifedipine (3HS + N) or hindlimb suspension + ouabain (3HS + Ou). It was found that functional unloading resulted in a decrease in the mass of m. soleus in all groups with functional unloading (3HS, 3HS + N, and 3HS + Ou) (p < 0.05). After 3-day hindlimb suspension without drugs, the cross-sectional area (CSA) of fast and slow muscle fibers (MF) decreased, the level of Ca2+ in the MF myoplasm increased, and the maximum strength of single and tetanic contractions of m. soleus decreased relative to the control (p < 0.05). Inhibition of DHPR during 3-day-long functional unloading prevented a decrease in CSA, a decrease in strength, an increase in the level of Ca2+ in the myoplasm of MF, and a decrease in the maximum strength of single and tetanic contraction of m. soleus. Upon the addition of ouabain, an increase in CSA and a decrease in the level of Ca2+ in the myoplasm were observed, while the specific (normalized by the physiological cross-section of the muscle) maximum force of single and tetanic contraction of m. soleus in animals decreased significantly compared to the group without drugs (3HS). However, ouabain significantly affected the passive mechanical properties of m. soleus, namely, the maximum peak force and maximum force at the end of the stretching test in muscles with the administration of the drug did not differ from the intact control group. Thus, the use of ouabain and nifedipine leads to the prevention of the accumulation of myoplasmic calcium under the functional unloading, which is accompanied by the preservation of specific stiffness and muscle strength, slowing the decrease in the cross-sectional area of MF and preventing a change in the percentage of MF towards fast-type fibers.