Diltiazem Improves Twitch Tension in Dysferlin‐Null BLAJ Mice but Does Not Reduce Contraction‐Induced Muscle Damage In Viv o

Background The L‐type Ca 2+ channel blocker diltiazem (DTZ) protects dysferlin‐null A/J mice from muscle damage induced by large‐strain eccentric contractions (20 repetitions) (1). One of the disadvantages of studying the A/J mouse strain is that, it does not have a true control mouse strain. Additionally, A/J mice carry several non‐dysferlin mutations that might have an effect on muscle function (2). BLAJ mice, which carry the same dysferlin mutation as A/J mice, albeit in the C57BL/6J background, show lesser muscle damage than A/J mice after large‐strain eccentric contractions (3). We therefore developed a new model of eccentric exercise (40 repetitions of medium‐strain eccentric contractions) that reliably induces sufficient damage in BLAJ mouse muscle, in order to test if DTZ blocks contraction‐induced muscle damage in BLAJ mice. Methods We studied the tibialis anterior (TA) muscle in 3–4 month old, male, dysferlin‐null BLAJ mice. We measured contractile torque and exposed the TA muscle to eccentric contractions (one bout; 40 repetitions; 90–160 □ plantarflexion superimposed on maximal tetany of ankle dorsiflexors) with a custom‐built dynamometer. For one group of mice (Vehichle, VEH, N = 6 mice), we gave intraperitoneal injections of distilled water, once daily, for one week prior to eccentric contractions and three days thereafter (10 ul per gram body weight). For another group of mice (DTZ, N = 6 mice), we gave intraperitoneal injections of DTZ (72 mg/kg/day), once daily, following a similar injection schedule as the VEH group (we dissolved 72 mg DTZ in 10 ml distilled water and injected 10 ul per gram body weight). We assessed baseline contractile torque, torque changes after eccentric contractions, and histology of unexercised and exercised TA muscles. Results Data are summarized in Table 1. DTZ improved Peak Twitch Torque, but did not provide protection against muscle damage from eccentric contractions. Conclusion Diltiazem might not offer protection against all types of contraction‐induced damage to dysferlin‐null muscle. Translational Relevance Diltiazem might not be able to protect muscles in patients with dysferlin deficiency if muscle damage exceeds a certain threshold level. Support or Funding Information This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .