Reversibility of high pressure effects on the contractility of skeletal muscle

High pressure application has been extensively used to thermodynamically in fluence complex physiological processes such as membrane ion conductances a nd the mechanism of muscle contraction. However, little is known about the reversibility of high pressure effects on intact cells. Therefore, we studi ed the reversibility of 3 h pressure applications up to 25 MPa at +4 degree sC to intact murine skeletal muscle. Functional mechanical properties were tested in extensor digitorum muscle fibres skinned following a high pressur e exposure. Calcium activated force and stiffness were nearly unchanged fol lowing pressure applications up to 20 MPa, whereas for higher pressures we found a marked reduction of peak force, a decline of activation kinetics, a n increase of relaxation stiffness but still unchanged peak stiffness. The rigor kinetics showed a similar behaviour as the activation kinetics. pCa-f orce relations remained unchanged up to 20 MPa but were shifted towards sma ller pCa values for higher pressures. In conclusion there is a rather sharp high pressure limit of 20 MPa above of which pressure application results in a substantial irreversible loss of contractile functionality in differen tiated muscle which may at least partly be explained by changes in the Ca2 regulatory process. This is supported by a degradation of the 37 kDa band, i.e. Troponin T, shown by SDS gel electrophoresis. However, the general st ability of the other bands does not indicate a substantial increase of unsp ecific protease activity following a high pressure treatment up to 25 MPa.