Stimulation of pulmonary C fibres by lactic acid in rats: Contributions of H⁺ and lactate ions

1. The contributions of H⁺ and lactate ions to the stimulation of single pulmonary C fibres by lactic acid were examined in anaesthetized and artificially ventilated rats. 2. Lactic acid injected into the right atrium caused a transient decrease in arterial blood pH (pH(a)) and a short but intense burst of afferent activities in pulmonary C fibres, whereas sodium lactate had no effect. The fibre activity usually reached a peak within 1-1.5 s, with an onset latency of < 1 s, and returned to the baseline in 5 s. 3. The injection of hydrochloric acid at the same pH as that of lactic acid did not significantly decrease pH(a), nor did it stimulate any C fibres studied. 4. Formic acid has a pK(a) value (the negative logarithm of the dissociation constant) almost identical to that of lactic acid; thus, its injection decreased pH(a) to the same degree as did the injection of lactic acid. However, the response of C fibres to lactic acid was 134% stronger than that to formic acid. 5. We conclude that H⁺ is primarily responsible for the activation of pulmonary C fibres by lactic acid, probably through a direct effect of H⁺ on these afferent endings. The lactate ion, by itself, does not activate C fibres, but it seems to potentiate the stimulatory effect of H⁺ on these afferents.