Excitability of oxytocin neurons in paraventricular nucleus is regulated by voltage-gated potassium channels Kv4.2 and Kv4.3

Biosci Biotechnol Biochem. 2019 Feb;83(2):202-211. doi: 10.1080/09168451.2018.1537773. Epub 2018 Nov 4.

Abstract

Oxytocin is produced by neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus in the hypothalamus. Various ion channels are considered to regulate the excitability of oxytocin neurons and its secretion. A-type currents of voltage-gated potassium channels (Kv channels), generated by Kv4.2/4.3 channels, are known to be involved in the regulation of neuron excitability. However, it is unclear whether the Kv4.2/4.3 channels participate in the regulation of excitability in PVN oxytocin neurons. Here, we investigated the contribution of the Kv4.2/4.3 channels to PVN oxytocin neuron excitability. By using transgenic rat brain slices with the oxytocin-monomeric red fluorescent protein 1 fusion transgene, we examined the excitability of oxytocin neurons by electrophysiological technique. In some oxytocin neurons, the application of Kv4.2/4.3 channel blocker increased firing frequency and membrane potential with extended action potential half-width. Our present study indicates the contribution of Kv4.2/4.3 channels to PVN oxytocin neuron excitability regulation. Abbreviation: PVN, paraventricular nucleus; Oxt-mRFP1, Oxt-monometric red fluorescent protein 1; PaTx-1, Phrixotoxin-1; TEA, Tetraethylammonium Chloride; TTX, tetrodotoxin; aCSF, artificial cerebrospinal fluid;PBS, phosphate buffered saline 3v, third ventricle.

Keywords: A-type current; Kv4.2; Kv4.3; oxytocin; paraventricular nucleus.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Female
  • Immunohistochemistry
  • Ion Channel Gating*
  • Luminescent Proteins / genetics
  • Male
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Oxytocin / metabolism*
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Rats, Transgenic
  • Rats, Wistar
  • Red Fluorescent Protein
  • Shal Potassium Channels / antagonists & inhibitors
  • Shal Potassium Channels / metabolism*
  • Spider Venoms / pharmacology

Substances

  • Luminescent Proteins
  • Potassium Channel Blockers
  • Shal Potassium Channels
  • Spider Venoms
  • phrixotoxin I, Phrixotrichus auratus
  • Oxytocin