Residual force enhancement is reduced in permeabilized fiber bundles from mdm muscles
Residual force enhancement (RFE) is the increase in steady-state force after active stretch relative to the force after isometric contraction at the same final length. The mdm mutation in mice, characterized by a small deletion in N2A titin, has been proposed to prevent N2A titin-actin interactions so that active mdm muscles are more compliant than WT. This decrease in active muscle stiffness should be associated with reduced RFE. We investigated RFE in permeabilized soleus (SOL) and extensor digitorum longus (EDL) fiber bundles from wild type and mdm mice. On each fiber bundle, we performed active and passive stretch from an average sarcomere length of 2.6 - 3.0 &[mu]m at a slow rate of 0.04 &[mu]m/s, as well as isometric contractions at the initial and final lengths. One-way ANOVA showed that SOL and EDL fiber bundles from mdm mice exhibited significantly lower RFE than WT (P < 0.0001). This result is consistent with previous observations in single myofibrils and intact muscles. However, it contradicts the results from a previous study which appeared to show that compensatory mechanisms could restore titin force enhancement in single fibers from mdm psoas. We suggest that force enhancement measured previously in mdm single fibers was an artifact of the high variability in passive tension found in degenerating fibers, which begins after ~24 days of age. The results are consistent with the hypothesis that RFE is reduced in mdm skeletal muscles due to impaired Ca2+ dependent titin-actin interactions resulting from the small deletion in N2A titin.