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.