Proceedings of The Physiological Society
University of Birmingham (2010) Proc Physiol Soc 20, PC33
Sternohyoid muscle function and MHC isoform expression in normoxic and chronically hypoxic rats during postnatal development
J. Carberry1, A. Bradford2, K. O'Halloran1
1. School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland. 2. Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
The upper airway muscles play a pivotal role in preventing airway collapse. Postnatal maturation is associated with major histochemical and biochemical changes in skeletal muscle which correlate with changes in muscle contractility. Perturbations to respiratory muscle during development such as exposure to chronic hypoxia (CH) may interfere with the normal maturational process. The functional/structural phenotype of the sternohyoid (SH) muscle during the neonatal period has not yet been classified and the effects of chronic hypoxia on respiratory muscles are largely unknown. Rat pups were raised under normoxic or hypoxic conditions at various postnatal ages during development (P9-P60). Animals were killed humanely by cervical dislocation and the paired SH muscles were surgically removed and cut into strips. SH contractile and endurance properties were assessed in vitro. Muscle fibre oxidative capacity was assessed by measurement of succinate dehydrogenase (SDH) activity. Myosin heavy chain (MHC) isoform expression was determined using monoclonal antibodies that identify MHC slow, 2a, 2x and 2b fibres. SH had significantly faster contractile kinetics and increased specific tension with advancing age (2.3 ± 0.4 vs. 11.7 ± 1.3 N/cm2, (mean ± SEM) peak tetanic force P9 (n=5) vs. P60 (n=8), P<0.05, one-way ANOVA. We observed dramatic age-related increases in muscle fatiguability. SH 5 minute fatigue index was 105 ± 5% vs. 24 ± 2 %, (% of initial force) P9 vs. P60, P<0.05. There was no age-related change in SH oxidative capacity. Muscle contractility was largely determined by developmental changes in MHC isoform expression. Areal density of MHC slow fibres was 10 ± 2 vs. 2 ± 1 %, P9 vs. P60 (P<0.05) whereas areal density of MHC 2b fibres was 1 ± 1 vs. 59 ± 3 %, P9 (n=6) vs. P60 (n=9), P<0.05. CH (450mmHg ambient pressure) increased SH muscle force in animals exposed to hypoxia for one week in early but not late development (e.g. peak force was 4.6 ± 1.1 vs. 8.2 ± 1.2 N/cm2 control (n=6) vs. CH (n=8), P<0.05 at P19 and 8.2 ± 1.3 vs. 10.6 ± 1.6 N/cm2 at P39 control (n=8) vs. CH (n=6). Functional remodelling in SH following CH was not attributable to changes in muscle oxidative capacity or MHC isoform expression. This study characterises the phenotypic profile of the SH from the neonatal period into adulthood. The results indicate that in rats the SH undergoes dramatic structural and functional remodelling in the first 2 months of postnatal life. Slow to fast fibre type transitions and decreased muscle endurance increases the vulnerability of the upper airway to collapse. Hypoxia-induced muscle plasticity may have implications for the control of airway patency in vivo.
Where applicable, experiments conform with Society ethical requirements