期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms232315334
关键词
locus coeruleus neurons; noradrenergic system; ERG K+ channels; ether-a-go-go-related gene; WAY-123; 398; class III anti-arrhythmic drug
资金
- United Arab Emirates University (UAEU)
- Malta Council for Science and Technology (MCST) Research Innovation [31M468, 31M452, 21M149]
- Alfred Mizzi Foundation through the RIDT, Malta [RI-2017-029T]
- [E17L077]
This study identified highly expressed ERG channel subunits in the LC that play a crucial role in modulating neuronal discharge patterns. Blocking the ERG channels increased the spontaneous firing activity and irregularity of LC neurons. Thus, ERG channels are important players in the generation and maintenance of LC firing patterns related to different behaviors and disorders.
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-a-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.
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