Impact of post-synaptic block of neuromuscular transmission, muscle unloading and mechanical ventilation on skeletal muscle protein and mRNA expression

• To analyse mechanisms of muscle wasting in intensive care unit patients, we developed an experimental model where rats were pharmacologically paralysed by post-synaptic block of neuromuscular transmission (NMB) and mechanically ventilated for 9 2 days. Specific interest was focused on the effects on protein and mRNA expression of sarcomeric proteins, i.e., myosin heavy chain (MyHC), actin, myosin-binding protein C (MyBP-C) and myosin-binding protein H (MyBP-H) in fast- and slow-twitch limb, respiratory and masticatory muscles. Muscle-specific differences were observed in response to NMB at both the protein and mRNA levels. At the protein level, a decreased MyHC-to-actin ratio was observed in all muscles excluding the diaphragm, whereas at the mRNA level a decreased expression of the dominating MyHC isoform(s) was observed in the hind limb and intercostal muscles, but not in the diaphragm and masseter muscles. MyBP-C mRNA expression was decreased in the limb muscles, but it otherwise remained unaffected. MyBP-H conversely increased in all muscles. Furthermore, we found myofibrillar protein and mRNA expression to be affected differently when comparing NMB; animals with peripherally denervated (DEN) ambulatory rats. We report that NMB; has both a larger and different impact on muscle, at the protein and mRNA levels, than DEN has.

Nyckelord

myosin

actin

neuromuscular blockade

immobilisation

mechanical ventilation

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MEDICIN

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