| First Author | Thekkedam CG | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 25 |
| Issue | 1 | PubMed ID | 38203604 |
| Mgi Jnum | J:344242 | Mgi Id | MGI:7573434 |
| Doi | 10.3390/ijms25010434 | Citation | Thekkedam CG, et al. (2023) The RyR1 P3528S Substitution Alters Mouse Skeletal Muscle Contractile Properties and RyR1 Ion Channel Gating. Int J Mol Sci 25(1) |
| abstractText | The recessive Ryanodine Receptor Type 1 (RyR1) P3527S mutation causes mild muscle weakness in patients and increased resting cytoplasmic [Ca(2+)] in transformed lymphoblastoid cells. In the present study, we explored the cellular/molecular effects of this mutation in a mouse model of the mutation (RyR1 P3528S). The results were obtained from 73 wild type (WT/WT), 82 heterozygous (WT/MUT) and 66 homozygous (MUT/MUT) mice with different numbers of observations in individual data sets depending on the experimental protocol. The results showed that WT/MUT and MUT/MUT mouse strength was less than that of WT/WT mice, but there was no difference between genotypes in appearance, weight, mobility or longevity. The force frequency response of extensor digitorum longus (EDL) and soleus (SOL) muscles from WT/MUT and MUT/MUT mice was shifter to higher frequencies. The specific force of EDL muscles was reduced and Ca(2+) activation of skinned fibres shifted to a lower [Ca(2+)], with an increase in type I fibres in EDL muscles and in mixed type I/II fibres in SOL muscles. The relative activity of RyR1 channels exposed to 1 microM cytoplasmic Ca(2+) was greater in WT/MUT and MUT/MUT mice than in WT/WT mice. We suggest the altered RyR1 activity due to the P2328S substitution could increase resting [Ca(2+)] in muscle fibres, leading to changes in fibre type and contractile properties. |
