Role of the JP45-calsequestrin complex on calcium entry in slow twitch skeletal muscles

We exploited a variety of mouse models to assess the roles of JP45/CASQ1 and JP45/CASQ2 on calcium entry in slow twitch muscles. In FDB fibres isolated from JP45/CASQ1/CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibres from WT, JP45KO, CASQ1KO, CASQ2KO, JP45/CASQ1 double KO, JP45/CASQ2 double KO and JP45/CASQ1/CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45/CASQ1 and JP45CASQ2 complexes supports tetanic force development in slow twitch Soleus muscles. In addition, we show that CASQs interact with JP45 at [Ca2+] similar to those present in the lumen of the sarcoplasmic reticulum at rest, while [Ca2+] similar to those present in the SR lumen after depolarisation-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45/CASQs is a negative regulator of ECCE, and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs.