Changes in junctophilin 1 contribute to strength deficits after eccentric contraction‐induced muscle injury

Abstract

Performance of eccentric contractions (ECCs) disrupts excitation‐contraction (E‐C) coupling and induces strength deficits. E‐C uncoupling may result from disturbance to the SR / t‐tubule triad structure. Junctophilin 1 (JP1) is a triadic protein that is thought to be required for normal voltage‐gated SR Ca++ release. We hypothesize that ECCs alter tibialis anterior (TA) muscle JP1 protein content and that functional recovery from ECCs corresponds to recovery of JP1. To test the hypothesis we compared strength and JP1 changes after ECCs in wild type (WT; n =12) and malignant hyperthermia susceptible (Y522S; n =12) mice that recover function after ECCs faster than WT mice. The left anterior crural muscles (primarily TA muscle) of Y522S and WT mice performed 150 ECCs and a pre‐ and 3 or 14d post‐injury torque‐frequency test, in vivo. JP1: tubulin protein content was determined in injured and uninjured TA muscles. 3d post‐injury, torque and JP1 were reduced similarly in both WT and Y522S mice. 14d post‐injury, torque and JP1 were recovered in Y522S mice, but were still reduced in WT mice. Regression analysis indicated that reductions of JP1 are strongly associated with torque deficits (r = 0.70). These results indicate that JP1 is reduced following ECCs and suggest that recovery of JP1 contributes to the restoration of prolonged torque deficits in TA muscle.‐Supported by NIH grant R01 AR41802 (S.L. Hamilton)