# Dihydropyridine Receptor Inhibition Attenuates Force and Fiber Cross-Sectional Area Decrease in the Three-Day Unloaded Rat Soleus Muscle

## TL;DR

Blocking a specific calcium channel in rat muscles prevents muscle atrophy during unloading by reducing calcium release and preserving muscle function.

## Contribution

This study shows that dihydropyridine receptor inhibition preserves muscle function during unloading by blocking calcium-dependent pathways.

## Key findings

- Nifedipine treatment prevents decreases in muscle contractile properties during unloading.
- DHPR inhibition reduces ATP, ROS, and Ca2+ accumulation in sarcoplasm and mitochondria.
- Blocking DHPR preserves PGC1alpha mRNA and prevents cytoskeletal protein degradation.

## 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.