Evans, Allison B., Larry W. Tsai, David A. Oelberg, Homayoun Kazemi, and David M. Systrom. Skeletal muscle ECF pH error signal for exercise ventilatory control. J. Appl. Physiol. 84(1): 90-96, 1998.An autonomic reflex linking exercising skeletal muscle metabolism to central ventilatory control is thought to be mediated by neural afferents having free endings that terminate in the interstitial fluid of muscle. To determine whether changes in muscle extracellular fluid pH (pH_e) can provide an error signal for exercise ventilatory control, pH_e was measured during electrically induced contraction by ³¹P-magnetic resonance spectroscopy and the chemical shift of a phosphorylated, pH-sensitive marker that distributes to the extracellular fluid (phenylphosphonic acid). Seven lightly anesthetized rats underwent unilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magnetic resonance magnet, which resulted in a mixed lactic acidosis and respiratory alkalosis, with no net change in arterial pH. Skeletal muscle intracellular pH fell from 7.30 ± 0.03 units at rest to 6.72 ± 0.05 units at 2.4 min of stimulation and then rose to 7.05 ± 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction. Despite arterial hypocapnia, pH_e showed an immediate drop from its resting baseline of 7.40 ± 0.01 to 7.16 ± 0.04 units (P < 0.05) and remained acidic throughout the stimulation protocol. During the on- and off-transients for 5-Hz stimulation, changes in the pH gradient between intracellular and extracellular compartments suggested time-dependent recruitment of sarcolemmal ion-transport mechanisms. pH_e of exercising skeletal muscle meets temporal and qualitative criteria necessary for a ventilatory metaboreflex mediator in a setting where arterial pH does not.