Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1

Gabriel Herrera-López, Emilio J. Galván*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


In addition to its prominent role as an energetic substrate in the brain, lactate is emerging as a signaling molecule capable of controlling neuronal excitability. The finding that the lactate-activated receptor (hydroxycarboxylic acid receptor 1; HCA1) is widely expressed in the brain opened up the possibility that lactate exerts modulation of neuronal activity via a transmembranal receptor-linked mechanism. Here, we show that lactate causes biphasic modulation of the intrinsic excitability of CA1 pyramidal cells. In the low millimolar range, lactate or the HCA1 agonist 3,5-DHBA reduced the input resistance and membrane time constant. In addition, activation of HCA1 significantly blocked the fast inactivating sodium current and increased the delay from inactivation to a conducting state of the sodium channel. As the observed actions occurred in the presence of 4-CIN, a blocker of the neuronal monocarboxylate transporter, the possibility that lactate acted via neuronal metabolism is unlikely. Consistently, modulation of the intrinsic excitability was abolished when CA1 pyramidal cells were dialyzed with pertussis toxin, indicating the dependency of a G αi/o -protein-coupled receptor. The activation of HCA1 appears to serve as a restraining mechanism during enhanced network activity and may function as a negative feedback for the astrocytic production of lactate.

Original languageEnglish (US)
Pages (from-to)557-567
Number of pages11
Issue number8
StatePublished - Aug 2018

Bibliographical note

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.


  • CA1 pyramidal cells
  • HCA1 receptor
  • hippocampus
  • intrinsic excitability
  • lactate

ASJC Scopus subject areas

  • Cognitive Neuroscience


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