Effects of extracellular HCO3− on fatigue, pHi, and K+ efflux in rat skeletal muscles

Elevated plasma HCO3− can improve exercise endurance in humans. This effect has been related to attenuation of the work-induced reduction in muscle pH, which is suggested to improve performance via at least two mechanisms: 1) less inhibition of muscle enzymes and 2) reduced opening of muscle KATP channels with less ensuing reduction in excitability. Aiming at determining whether the ergogenic effect of HCO3− is related to effects on muscles, we examined the effect of elevating extracellular HCO3− from 25 to 40 mM (pH from 7.4 to 7.6) on fatigue, intracellular pH (pHi), and K+ efflux in isolated rat skeletal muscles contracting isometrically. Fatigue induced by 30-Hz stimulation at 30 and 37°C was similar between soleus muscles incubated in high and normal HCO3− concentrations. In extensor digitorum longus muscles stimulated at 60 Hz, elevated HCO3− did not affect fatigue at 30°C. In soleus muscles, 30-Hz stimulation induced a ∼0.2 unit reduction in pHi, as determined by using the pH-sensitive probe 2′,7′-bis(2-carboxyethyl)-5( 6 )-carboxyfluorescein. This reduction in pHi was not affected by elevated HCO3−. Estimation of K+ efflux using 86Rb+ showed that elevated HCO3− did not affect K+ efflux at rest or during contractions. Similarly, other modifications of the intra- and extracellular pH had little effect on K+ efflux during contraction. In conclusion, elevated extracellular HCO3− had no significant effect on muscle fatigue, pHi, and K+ efflux. These findings indicate that alternative mechanisms must be considered for the ergogenic effect of HCO3− observed in integral exercise studies.