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

Elevated plasma HCO(3)(-) 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 K(ATP) channels with less ensuing reduction in excitability. Aiming at determining whether the ergogenic effect of HCO(3)(-) is related to effects on muscles, we examined the effect of elevating extracellular HCO(3)(-) from 25 to 40 mM (pH from 7.4 to 7.6) on fatigue, intracellular pH (pH(i)), and K(+) efflux in isolated rat skeletal muscles contracting isometrically. Fatigue induced by 30-Hz stimulation at 30 and 37 degrees C was similar between soleus muscles incubated in high and normal HCO(3)(-) concentrations. In extensor digitorum longus muscles stimulated at 60 Hz, elevated HCO(3)(-) did not affect fatigue at 30 degrees C. In soleus muscles, 30-Hz stimulation induced a approximately 0.2 unit reduction in pH(i), as determined by using the pH-sensitive probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. This reduction in pH(i) was not affected by elevated HCO(3)(-). Estimation of K(+) efflux using (86)Rb(+) showed that elevated HCO(3)(-) 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 HCO(3)(-) had no significant effect on muscle fatigue, pH(i), and K(+) efflux. These findings indicate that alternative mechanisms must be considered for the ergogenic effect of HCO(3)(-) observed in integral exercise studies.