Kv4.2 Mediates Histamine Modulation of Preoptic Neuron Activity and Body Temperature

PLoS One. 2011;6(12):e29134. doi: 10.1371/journal.pone.0029134. Epub 2011 Dec 29.

Abstract

Histamine regulates arousal, circadian rhythms, and thermoregulation. Activation of H3 histamine receptors expressed by preoptic GABAergic neurons results in a decrease of their firing rate and hyperthermia. Here we report that an increase in the A-type K⁺ current in preoptic GABAergic neurons in response to activation of H3 histamine receptors results in decreased firing rate and hyperthermia in mice. The Kv4.2 subunit is required for these actions in spite of the fact that Kv4.2⁻/⁻ preoptic GABAergic neurons display A-type currents and firing characteristics similar to those of wild-type neurons. This electrical remodeling is achieved by robust upregulation of the expression of the Kv4.1 subunit and of a delayed rectifier current. Dynamic clamp experiments indicate that enhancement of the A-type current by a similar amount to that induced by histamine is sufficient to mimic its robust effect on firing rates. These data indicate a central role played by the Kv4.2 subunit in histamine regulation of body temperature and its interaction with pERK1/2 downstream of the H3 receptor. We also reveal that this pathway provides a mechanism for selective modulation of body temperature at the beginning of the active phase of the circadian cycle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology*
  • Circadian Rhythm / drug effects
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism
  • Histamine / metabolism*
  • Histamine Agonists / pharmacology
  • Injections
  • Ion Channel Gating / drug effects
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neurons
  • Patch-Clamp Techniques
  • Preoptic Area / cytology
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism
  • Preoptic Area / physiology*
  • Protein Subunits / metabolism
  • Receptors, Histamine H3 / metabolism
  • Shal Potassium Channels / deficiency
  • Shal Potassium Channels / metabolism*
  • Spider Venoms / administration & dosage
  • Spider Venoms / pharmacology
  • Up-Regulation / drug effects

Substances

  • Histamine Agonists
  • Protein Subunits
  • Receptors, Histamine H3
  • Shal Potassium Channels
  • Spider Venoms
  • phrixotoxin I, Phrixotrichus auratus
  • Histamine