EFFECTS OF HYPOXIA ON DIAPHRAGM RELAXATION RATE DURING FATIGUE

Skeletal muscle fatigue is associated with a slowing of relaxation rat e. Hypoxia may increase the rate at which fatigue occurs, but, surpris ingly, mild to moderate hypoxia has not been found to augment the degr ee of slowing of relaxation during fatigue. The present study tested t he hypothesis that severe hypoxia interacts with fatigue in slowing th e rate of muscle relaxation and that this can be modulated by altering membranous ionic conductances. Rat diaphragm muscle strips were studi ed in vitro while aerated with 95% O-2-5% CO2 (normoxia) or 95% N-2-5% CO2 (hypoxia). During continuous 0.1-Hz stimulation, relaxation rate and force remained stable over time, and relaxation rate was not slowe d by hypoxia. Hypoxia accelerated force decline during continuous 5-Hz but not intermittent 20-Hz stimulation. During both 5- and 20-Hz stim ulation, relaxation rate became slower over time as force declined, th e extent of which was increased significantly by hypoxia. The extent o f hypoxia-augmented slowing of relaxation rate during fatigue increase d over time and was greater than expected for a given degree of force loss. 4-Aminopyridine did not attenuate or partially attenuated, where as lowering extracellular Cl- concentration fully attenuated, the hypo xia-induced prolongation of relaxation rate during repetitive stimulat ion. Thus hypoxia slows relaxation rate to a greater extent than expec ted for a given degree of force decline, an effect that increases over time, is at most partially attenuated by lowering K+ conductance, and is fully attenuated by lowering membranous Cl- conductance.