Developmental induction of DHPR alpha 1s and RYR1 gene expression does not require neural or mechanical signals.

This study compares dihydropyridine receptor (DHPR) and ryanodine receptor (RyR1) gene expression in the diaphragm and hindlimb skeletal muscles of neonatal mice, and examines the contribution of neural and mechanical signals to their developmental induction in vivo. DHPR alpha 1s subunit and RyR1 protein are expressed concurrently, while their respective mRNAs are induced sequentially, with DHPR mRNA ahead of RyR1 mRNA. Both DHPR and RyR1 are more abundant in the diaphragm at birth, and become more abundant in the hindlimb at maturity. These patterns are consistent across different muscles and species. A critical period for DHPR alpha 1s and RyR1 gene expression in the hindlimb occurs between days 5 and 19 postnatal. Their mRNA expression during this period is unchanged by denervation or tenotomy, but DHPR protein decreases after tenotomy. These results demonstrate that both transcriptional and post-transcriptional mechanisms contribute to the muscle-specific and coordinated assembly of the functional DHPR-RyR1 complex, and that the developmental induction of DHPR and RyR1 gene transcription does not require neural or mechanical signals.