Fig. 6: Separate lactate- and O₂-sensing mechanisms in glomus cells.

a Amperometric recording illustrating the secretory response to lactate (20 mM, gray) in the presence of rotenone (1 μM). Similar recordings were obtained in 7 cells from 3 mice. b, c NADH signals induced by lactate (Lac, 10 mM; gray) in a hypoxia (Hx, O₂ tension ≈15 mm Hg; pale blue)-insensitive glomus cell dispersed from a Ndufs2-deficient CB. Box plots representing the distribution of changes in NADH signals (ΔNADH) in 22 cells from 3 mice exposed to the two stimuli. In these experiments, all cells responded to lactate (10 mM) but only 40% of the cells showed some responsiveness to hypoxia (O₂ tension ≈15 mm Hg). Mean ± SEM values are: 10 mM lactate: 52.5 ± 4.3; hypoxia: 28.2 ± 3.2. P value calculated by two tails, unpaired t test is indicated. The boxplot represents the median (middle line), 25th, 75th percentile (box), and largest and smallest values extending no further than 1.5 × interquartile range (whiskers). Source data are provided as a Source data file. d, e Representative amperometric recordings from an Ndufs2-deficient CB slice showing that cells insensitive to hypoxia (pale blue) are activated by lactate (10 mM, gray), hypercapnia (10% CO₂, pale red) and K⁺ (40 mM)-induced depolarization. Similar experiments (n = 6) were performed in CBs from 3 mice. None of the cells from these mice showed a secretory response to hypoxia. f Secretory responses to lactate (gray) in a hypoxia-insensitive (pale blue) glomus cell deficient of the Epas1 (coding Hif2α) gene. Similar experiments (n = 2) were performed in CBs from two mice. g Schematic representation of the major compartmentalized steps in acute oxygen and lactate sensing by carotid body glomus cells. The decrease of oxygen (hypoxia) is detected by mitochondria, giving rise to the production of NADH (N) and reactive oxygen species (R) which inhibit nearby membrane K⁺ channels to induce depolarization. On the other hand, lactate is transported into the cells by MCTs and rapidly converted to pyruvate with the production of NADH, which activates membrane cation channels to produce cell depolarization (an effect that may be facilitated by intracellular acidification). Pyruvate can also increase the production of reactive oxygen species at the mitochondria and in this manner contribute to the activation of glomus cells. Both hypoxia and lactate increase cytosolic [Ca²⁺] and induce transmitter release. MCT monocarboxylate transporter, LDH lactate dehydrogenase, ΔVm membrane depolarization. Arbitrary units (arb. units).