SK channels control the firing pattern of midbrain dopaminergic neurons in vivo
Abstract
A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K+ channels of the SK type. However, due to the lack of suitable tools, in vivo evidence is lacking. We have taken advantage of the development of the water-soluble, medium potency SK blocker N-methyl-laudanosine (CH3-L) to test this hypothesis in anaesthetized rats. In the lateral ventral tegmental area, CH3-L iontophoresis onto dopaminergic neurons significantly increased the coefficient of variation of their interspike intervals and the percentage of spikes generated in bursts as compared to the control condition. The effect of CH3-L persisted in the presence of a specific GABA(A) antagonist, suggesting a direct effect. It was robust and reversible, and was also observed in the substantia nigra. Control experiments demonstrated that the effect of CH3-L could be entirely ascribed to its blockade of SK channels. On the other hand, the firing pattern of noradrenergic neurons was much less affected by CH3-L. We provide here the first demonstration of a major role of SK channels in the control of the switch between tonic and burst firing of dopaminergic neurons in physiological conditions. This study also suggests a new strategy to develop modulators of the dopaminergic (DA) system, which could be of interest in the treatment of Parkinson's disease, and perhaps other diseases in which DA pathways are dysfunctional.
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Lack of changes in SK current densities and lack of changes in the regularity of firing show that differences, if any, between genotypes are too small to be detectable.
“However, lack of changes in SK current densities and lack of changes in the regularity of firing (Ji and Shepard, 2006; Waroux et al., 2005) show that differences, if any, between genotypes are too small to be detectable.”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Waroux et al., 2005
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“However, lack of changes in SK current densities and lack of changes in the regularity of firing (Ji and Shepard, 2006; Waroux et al., 2005) show that differences, if any, between genotypes are too small to be detectable.”
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- Authors
- Waroux, O., Massotte, L., Alleva, L., Graulich, A., Thomas, E., Liégeois, J., Scuvée‐Moreau, J., & Seutin, V.
- Affiliations
- University of Liège (BE)
- Corresponding author
- Seutin, Vincent
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-12
- Volume
- 22
- Issue
- 12
- Pages
- 3111-3121
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2095427325
- Cited by
- 103
- References
- 48
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 13 · 2013: 6 · 2012: 8
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- ORBi (University of Liège) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- small conductance calcium-activated potassium channels, midbrain dopaminergic neurons, burst firing, tonic firing, firing patterns, substantia nigra, ventral tegmental area, noradrenergic neurons, GABAA receptor, Parkinson's disease
- MeSH terms
- Action Potentials, Alkanes, Analysis of Variance, Animals, Dopamine, Drug Interactions, gamma-Aminobutyric Acid, Iontophoresis, Isoquinolines, Male, Mesencephalon, Neurons, Oxotremorine, Pyridazines, Quinolinium Compounds, Rats, Wistar, Muscarinic Agonists, GABA Antagonists, Rats, Small-Conductance Calcium-Activated Potassium Channels, In Vitro Techniques
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