Stretch-induced membrane damage in muscle: comparison of wild-type and mdx mice.

ABSTRACT

One component of stretch-induced muscle damage is an increase in the permeability of the cell membrane. As a result soluble myoplasmic proteins leak out of the muscle into the plasma, extracellular proteins can enter the muscle, and extracellular ions, including calcium, are driven down their electrochemical gradient into the myoplasm. In Duchenne muscular dystrophy, caused by the absence of the cytoskeletal protein dystrophin, stretch-induced membrane damage is much more severe. The most popular theory to explain the occurrence of stretch-induced membrane damage is that stretched-contractions cause transient mechanically-induced defects in the membrane (tears or rips). Dystrophin, which is part of a mechanical link between the contractile machinery and the extracellular matrix, is thought to contribute to membrane strength so that in its absence mechanically-induced defects are worse. In our view the evidence that stretch-induced muscle damage causes increased membrane permeability is overwhelming but the evidence that the increased permeability is caused by mechanically-induced defects is weak. Instead we review the substantial evidence that the membrane permeability is a secondary consequence of the mechanical events in which elevated intracellular calcium and reactive oxygen species are important intermediaries.