Abstract: During muscle unloading accumulation of macroergic phosphates and Ca2+ ions occur in muscle fibers. Soleus unloading reduces the resting membrane potential, which is accompanied by the accumulation of [Ca2+] in the sarcoplasm. ATP that ends up in the extracellular space can induce a delayed slow release of Ca2+ in the myoplasm via the P2Y2-PLC-IP3. We tested the hypothesis about a relationship between changes in cellular [Ca2+] concentration, ATP accumulation and activation of the IP3-dependent signaling pathway during soleus unloading. 3 experiments were carried out: 1. with inhibition of L-type channels by nifedipine and 2. Inhibition of IP3-kinase, 3. Inhibition of IP3 receptors during soleus unloading of Wistar rats. It was found that during soleus unloading: 1. blocking DHPR prevents an increase in ATP and [Ca2+] levels in the myoplasm (p<0.05) 2. inhibition of PI3K slows down m. soleus atrophy, prevents ATP accumulation in it, expression of ubiquitin ligase MuRF1 and Ub, an increase in IP3 levels and IP3R expression, an increase in the expression of Ca-dependent mRNA CaN, prevents a decrease in pCaMKII (Ca-calmodulin kinase II) (p<0.05); affects the regulation of anabolic signaling markers in unloaded muscles (IRS1 and 4E-BP); 3. inhibition of IP3 receptors prevents a decrease in the cross-sectional area of the m. soleus of fast and slow muscle fibers, which is associated with the prevention of a decrease in ribosomal biogenesis and an increase in the expression of autophagy markers ULK-1 and IL-6 (p<0.05). A decrease in Ca-dependent pCaMKII was prevented. Conclusion: There is a relationship between Ca influx into the fiber, ATP content and soleus atrophy. IP3K and IP3R are involved in the regulation of signaling during skeletal muscle unloading.

Cite: Nemirovskaya T.L. , Zaripova K.A. , Belova S.P. , Sharlo K.A.
The IP3-dependent signaling pathway is involved in the regulation of atrophic processes in skeletal muscles during their unloading
Biomembranes 2024 07-11 Oct 2024