- Title
- Crosstalk between mitochondria, calcium channels and actin cytoskeleton modulates noradrenergic activity of locus coeruleus neurons
- Creator
- de Oliveira, Ramatis B.; Petiz, Lyvia L.; Lim, Rebecca; Lipski, Janusz; Gravina, Fernanda S.; Brichta, Alan M.; Callister, Robert J.; Leão, Richardson N.; van Helden, Dirk F.
- Relation
- Journal of Neurochemistry Vol. 149, Issue 4, p. 471-487
- Publisher Link
- http://dx.doi.org/10.1111/jnc.14692
- Publisher
- Wiley
- Resource Type
- journal article
- Date
- 2019
- Description
- Locus coeruleus (LC) is the name of a group of large sized neurons located at the brain stem, which provides the main source of noradrenaline to the central nervous system, virtually, innervating the whole brain. All noradrenergic signalling provided by this nucleus is dependent on an intrinsic pacemaker process. Our study aims to understand how noradrenergic neurons finely tune their pacemaker processes and regulate their activities. Here we present that mitochondrial perturbation in the LC from mice, inhibits spontaneous firing by a hyperpolarizing response that involves Ca²⁺ entry via L-type Ca²⁺ channels and the actin cytoskeleton. We found that pharmacological perturbation of mitochondria from LC neurons using the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), induced a dominant hyperpolarizing response when electrophysiological approaches were performed. Surprisingly, the CCCP-induced hyperpolarizing response was dependent on L-type Ca²⁺ channel-mediated Ca²⁺ entry, as it was inhibited by: the removal of extracellular Ca²⁺ ; the addition of Cd²⁺ ; nifedipine or nicardipine; but not by the intracellular dialysis with the Ca²⁺ chelator 1,2-Bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, the latter indicating that the response was not because of a global change in [Ca²⁺]c but does not exclude action at intracellular microdomains. Further to this, the incubation of slices with cytochalasin D, an agent that depolymerises the actin cytoskeleton, inhibited the hyperpolarizing response indicating an involvement of the actin cytoskeleton. The data are consistent with the hypothesis that there is a crosstalk between mitochondria and L-type Ca²⁺ channels leading to modulation of noradrenergic neuronal activity mediated by the actin cytoskeleton.
- Subject
- actin cytoskeleton; calcium channels; locus coeruleus; mitochondria; neuronal activity; noradrenergic
- Identifier
- http://hdl.handle.net/1959.13/1410645
- Identifier
- uon:36209
- Identifier
- ISSN:0022-3042
- Rights
- This is the peer reviewed version of the above article, which has been published in final form at: https://doi.org/10.1111/jnc.14692. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
- Language
- eng
- Full Text
- Reviewed
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