Locus Coeruleus Neurons’ Firing Pattern Is Regulated by ERG Voltage-Gated K+ Channels

Sonia Hasan, Francis Delicata, Leonardo Guasti, Claudia Duranti, Fatemah Mousalem Haidar, Annarosa Arcangeli, Paola Imbrici, Mauro Pessia, Mario Valentino, Maria Cristina D’Adamo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Locus coeruleus (LC) neurons, with their extensive innervations throughout the brain, control a broad range of physiological processes. Several ion channels have been characterized in LC neurons that control intrinsic membrane properties and excitability. However, ERG (ether-à-go-go–related gene) K+ channels that are particularly important in setting neuronal firing rhythms and automaticity have not as yet been discovered in the LC. Moreover, the neurophysiological and pathophysiological roles of ERG channels in the brain remain unclear despite their expression in several structures. By performing immunohistochemical investigations, we found that ERG-1A, ERG-1B, ERG-2 and ERG-3 are highly expressed in the LC neurons of mice. To examine the functional role of ERG channels, current-clamp recordings were performed on mouse LC neurons in brain slices under visual control. ERG channel blockade by WAY-123,398, a class III anti-arrhythmic agent, increased the spontaneous firing activity and discharge irregularity of LC neurons. Here, we have shown the presence of distinct ERG channel subunits in the LC which play an imperative role in modulating neuronal discharge patterns. Thus, we propose that ERG channels are important players behind the changes in, and/or maintenance of, LC firing patterns that are implicated in the generation of different behaviors and in several disorders.

Original languageEnglish
Article number15334
JournalInternational journal of molecular sciences
Volume23
Issue number23
DOIs
Publication statusPublished - Dec 2022

Keywords

  • ERG K channels
  • WAY-123,398
  • class III anti-arrhythmic drug
  • ether-à-go-go–related gene
  • locus coeruleus neurons
  • noradrenergic system

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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