Abstract: The depolarization of the sarcolemma is one of the first effects of unloading on skeletal muscle. We hypothesized that unloading-induced activation of the dihydropyridine receptor (DHPR), a voltage-sensitive L-type Ca2+ channel, and depolarization of the sarcolemma trigger intracellular Ca2+ release from the sarcoplasmic reticulum and activation of Ca2+-dependent signaling pathways, resulting in muscle atrophy. Nifedipine, a DHPR calcium channel blocker, was used to study the role of DHPR in the regulation of signaling pathways during three days of rat soleus muscle unloading/hindlimb suspension. Inhibition of the DHPR during unloading attenuates the decrease in soleus muscle contractile properties, prevents the accumulation of ATP, ROS, and Ca2+ content in the sarcoplasm and the mitochondria, and blocks the decrease in PGC1alpha mRNA expression and Junctophilin-1 (JP1) proteolysis. In nifedipine-treated rats, the improvement of the unloaded soleus muscle contractile properties could be mediated by blocking the calpain-mediated degradation of the cytoskeletal proteins. DHPR blocking could be one of the future directions for the preservation of contractile properties of inactive/unloaded muscle.

Cite: Sharlo K.A. , Tyganov S.A. , Sidorenko D.A. , Bokov R.O. , Zaripova K.A. , Kostrominova T.Y. , Shenkman B.S. , Nemirovskaya T.L.
Dihydropyridine Receptor Inhibition Attenuates Force and Fiber Cross-Sectional Area Decrease in the Three-Day Unloaded Rat Soleus Muscle
International Journal of Molecular Sciences. 2026. V.27. N4. 2043 :1-19. DOI: 10.3390/ijms27042043 OpenAlex

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W7130925909

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