ABSTRACT
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: J.M.S.; Formal analysis: J.M.S.; Investigation: M.T.B., J.M.S.; Data curation: M.T.B., J.M.S.; Writing - original draft: J.M.S.; Writing - review & editing: J.M.S.; Visualization: J.M.S.; Supervision: J.M.S.; Project administration: J.M.S.; Funding acquisition: J.M.S.
Funding
This work was funded in part by a grant from the National Institutes of Health (R15NS112920), as well as laboratory startup funds from the University of North Carolina at Greensboro to J.M.S. Deposited in PMC for release after 12 months.
Supplementary information
Supplementary information available online at https://jeb.biologists.org/lookup/doi/10.1242/jeb.235705.supplemental
- Received August 15, 2020.
- Accepted November 3, 2020.
- © 2020. Published by The Company of Biologists Ltd
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