Apr 29, 2018

Modulation of hippocampal excitability via the hydroxycarboxylic acid receptor 1

Hippocampus
Gabriel Herrera-López, Emilio J Galván

Abstract

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 Gαi/o -protein-coupled receptor. The activation of HCA1 appears to serve as a ...Continue Reading

  • References47
  • Citations2

References

  • References47
  • Citations2

Citations

Mentioned in this Paper

Metabolic Process, Cellular
Signaling Molecule
Potassium Channel Blockers
Exertion
CA1 Pyramidal Cell Area
Lactate
Membrane
G-Protein-Coupled Receptors
Toxin
Neurons

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