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Effect of botulinum toxin A‐induced paralysis and exercise training on mechanosensing and signalling gene expression in juvenile rat gastrocnemius muscle
Author(s) -
Velders Martina,
Legerlotz Kirsten,
Falconer Shelley J.,
Stott N. Susan,
McMahon Christopher D.,
Smith Heather K.
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2008.043174
Subject(s) - myod , gastrocnemius muscle , endocrinology , medicine , skeletal muscle , titin , biology , anatomy , chemistry , sarcomere , myocyte , myogenesis
Intramuscular injections of the paralytic botulinum neurotoxin A (Btx) and physical exercise are used in the treatment of chronic spasticity in children with cerebral palsy. We tested whether Btx‐induced paralysis and/or exercise training would have differential effects on the expression of mechanosensing and signalling genes implicated in the adaptive remodelling of skeletal muscle. Juvenile (29‐day‐old) male rats were injected with Btx or saline (NoBtx) into the right gastrocnemius and housed in standard cages (NoEx) or with running wheels (Ex), for 3 weeks ( n = 6 per group). The mRNA expression of nine sarcomere‐associated genes in the medial gastrocnemius was then determined by quantitative reverse transcriptase‐polymerase chain reaction. The Btx‐injected muscles weighed 50% less than NoBtx muscles, but Ex had no effect on the wet mass of Btx or NoBtx muscles. Atrogenic MuRF1 , sarcomeric Titin and myogenic MyoD were upregulated (2‐fold) with the elimination of contractile activity in Btx muscle. Expression of CARP , Ankrd2 and MLP was increased with mechanical stimuli associated with Btx (5‐ to 10‐fold) or Ex (2‐ to 4‐fold). Expression of CARP and Ankrd2 increased synergistically in Btx–Ex muscle (≥20‐fold), indicating that these genes may be sensitive to passive stretch of the sarcomeric I‐band region of titin to which their proteins bind. Tcap , Myopalladin and Atrogin1 were not, or were no longer responsive to the altered mechanical stimuli after 3 weeks of Btx or Ex. The expression of Ankrd2 , CARP and MLP may thus be enhanced by passive stretch within the Btx‐paralysed and/or exercising gastrocnemius and contribute to adaptations, other than muscle mass, in juvenile rats.