A direct excitatory action of lactate ions in the central respiratory network of bullfrogs, Lithobates catesbeianus.

Chemoreceptors that detect O2 and CO2/pH regulate ventilation. However, recent work shows that lactate ions activate arterial chemoreceptors independent of pH to stimulate breathing. Although lactate rises in the central nervous system (CNS) during metabolic challenges, the ability of lactate ions to enhance ventilation by directly targeting the central respiratory network remains unclear. To address this possibility, we isolated the amphibian brainstem-spinal cord and found that small increases in CNS lactate stimulate motor output that causes breathing. In addition, lactate potentiated the excitatory postsynaptic strength of respiratory motor neurons, thereby coupling central lactate to the excitatory drive of neurons that trigger muscle contraction. Lactate did not affect motor output through pH or pyruvate metabolism, arguing for sensitivity to lactate anions per se. In sum, these results introduce a mechanism whereby lactate ions in the CNS match respiratory motor output to metabolic demands.