Author(s): HANDEGARD, V., ØRSTAVIK, K.2, LUNDE, P.K.3, SEYNNES, O.1, PAULSEN, G.1, LOUCH, W.E.3, RAASTAD, T.1, Institution: NORWEGIAN SCHOOL OF SPORT SCIENCES, Country: NORWAY, Abstract-ID: 2440

INTRODUCTION:
Myotonic Dystrophy type I (DM1) is the most common adult-onset muscular dystrophy and patients presents with muscle weakness. DM1 skeletal muscle show reduced expression of central Ca2+ handling proteins, such as the Ryanodine Receptor (RyR; 1) and the Sarcoplasmic Reticulum (SR) Ca2+ ATPase (SERCA; 2). Increased intracellular resting levels of Ca2+ has been shown in DM1 myotubes (1). Together these findings indicate disrupted Ca2+ homeostasis. The aims of this study were therefore to (1) establish if SR Ca2+ handling is different in DM1 patients compared to healthy controls, and (2) investigate if resistance exercise (RE) could alter SR Ca2+ handling in DM1 patients.
METHODS:
DM1 patients (DM1) and healthy controls (Ctrl) underwent three bouts of unilateral moderate-heavy RE (leg press and knee extension), with 72 hours of recovery between bouts. Maximal force (MVC) of the knee extensors was measured at baseline and 5 minutes, 3, 24, 48, and 72 hours after bout 1, 72 hours after bout 2 and 24 hours after bout 3. M. vastus lateralis biopsies were obtained at baseline and 24 hours after bout 3. SR Ca2+ handling was investigated using a SR vesicle preparation. Muscle tissue homogenate was analysed for RyR, SERCA1a, SERCA2, Phospholamban (PLB; total and phosphorylated) expression using Western blotting. Baseline data were investigated with one-way ANOVA or t-test. Effects of RE were analysed with a mixed model with time and disease as fixed effects. Data are expressed as mean ± standard deviation.
RESULTS:
MVC was not different between DM1 and Ctrls at baseline. DM1 had higher Ca2+ uptake rates than Ctrls, with no differences between DM1 and Ctrls in Ca2+ release rates. DM1 also showed higher SR Ca2+ load compared to Ctrls. No baseline differences were detected in expression of SERCA1a, SERCA2, PLB, p-PLB, or RyR, although p-PLB/PLB ratio tended to be higher in DM1 (p=0.068). MVC was reduced by 14 % 3 hours after RE in DM1 (p=0.037), before returning to baseline whereas Ctrls increased from baseline to 24 h after RE (p=0.031). The groups were not significantly different from each other at any time point. Maximal Ca2+ uptake rate decreased after three bouts of RE in DM1 (p=0.01), while Ctrls were unchanged. The Ca2+ release rate was higher in DM1 compared to Ctrls after RE (p=0.04). DM1 showed lower p-PLB compared to Ctrls after RE (p=0.004). None of the other proteins investigated changed expression after RE.
CONCLUSION:
DM1 had a higher Ca2+ uptake rate and a higher SR Ca2+ load at baseline compared to Ctrls. We speculate if p-PLB play a role in the different Ca2+ uptake rate between DM1 and Ctrls. The acute MVC reduction in DM1 indicate a slightly lower exercise tolerance compared to Ctrls, however DM1 still recovered after 24 hours. Interestingly three bouts of RE seem to have a normalizing effect on SR Ca2+ uptake rate in DM1 patients which could be explained by a reduction in p-PLB.
(1) Santoro et al., 2020
(2) Ravel-Chapuis et al., 2017