An autonomic reflex linking exercising skeletal muscle metabolism to c
entral ventilatory control is thought to be mediated by neural afferen
ts having free endings that terminate in the interstitial fluid of mus
cle. 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 P-31-magnet
ic resonance spectroscopy and the chemical shift of a phosphorylated,
pH-sensitive marker that distributes to the extracellular fluid (pheny
lphosphonic acid). Seven lightly anesthetized rats underwent unilatera
l continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magne
tic resonance magnet, which resulted in a mixed lactic acidosis and re
spiratory alkalosis, with no net change in arterial pH. Skeletal muscl
e 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 uni
ts (P < 0.05), despite ongoing stimulation and muscle contraction. Des
pite arterial hypocapnia, pH(e) showed an immediate drop from its rest
ing baseline of 7.40 +/- 0.01 to 7.16 +/- 0.04 units (P < 0.05) and re
mained acidic throughout the stimulation protocol. During the on-and o
ff-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 exercis
ing skeletal muscle meets temporal and qualitative criteria necessary
for a ventilatory metaboreflex mediator in a setting where arterial pH
does not.