Asynchronous functional, cellular and transcriptional changes after a bout of eccentric exercise in the rat.

Peters D, Barash IA, Burdi M, Yuan PS, Mathew L, Fridén J, Lieber RL.

J Physiol., 2003 553(3): 947-957.

Abstract:

Thirty eccentric contractions (ECs) were imposed upon rat dorsiflexors (n=46) by activating the peroneal nerve and plantarflexing the foot ~40°, corresponding to a sarcomere length change over the range 2.27-2.39 µm for the tibialis anterior and 2.52-2.66 µm for the extensor digitorum longus. Animals were allowed to recover for one of ten time periods ranging from 0.5 to 240 hours, at which time muscle contractile properties, immunohistochemical labeling and gene expression were measured. Peak isometric torque dropped significantly by ~40% from an initial level of 0.0530±0.0009 Nm to 0.0298±0.0008 Nm (p<0.0001) immediately after EC and then recovered in a linear fashion to control levels 168 hours later. Immunohistochemical labeling of cellular proteins revealed a generally asynchronous sequence of events at the cellular level, with the earliest event measured being loss of immunostaining for the intermediate filament protein, desmin. Soon after first signs of desmin loss was infiltration of inflammatory cells followed by a transient increase in membrane permeability, manifest as inclusion of plasma fibronectin. The quantitative polymerase chain reaction (QPCR) was used to measure transcript levels of desmin, vimentin, embryonic MHC, myostatin, MyoD and myogenin. Compared to control levels, myostatin transcripts were significantly elevated after only 0.5 hours, myogenic regulatory factors significantly elevated after 3 hours and desmin transcripts were significantly increased 12 hours after EC. None of the measured parameters provide a mechanistic explanation for muscle force loss after EC. Future studies are required to investigate whether there is a causal relationship among desmin loss, increased cellular permeability, upregulation of the MyoD and desmin genes, and, ultimately, an increase in the desmin content per sarcomere of the muscle.

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