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Sci Rep. 2019 Feb 28;9(1):3112. doi: 10.1038/s41598-019-39703-3.

Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons.

Candelas M1,2,3,4, Reynders A5, Arango-Lievano M2,3,4, Neumayer C1,2,3,4, Fruquière A1,2,3,4, Demes E1,2,3,4, Hamid J6, Lemmers C1,2,3,7, Bernat C1,2,3,7, Monteil A1,2,3,4,7, Compan V1,2,3,4, Laffray S1,2,3,4, Inquimbert P8, Le Feuvre Y9, Zamponi GW6, Moqrich A5, Bourinet E10,11,12,13, Méry PF14,15,16,17.

Author information

1
Laboratories of Excellence - Ion Channel Science and Therapeutics, Montpellier, France.
2
Inserm U-1191, Montpellier, France.
3
CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.
4
Université Montpellier, Montpellier, France.
5
Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de, Marseille, France.
6
Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
7
Plateforme de Vectorologie, Biocampus Montpellier, CNRS UMS 3426, INSERM US009, Montpellier, France.
8
CNRS, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
9
UMR 5297, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
10
Laboratories of Excellence - Ion Channel Science and Therapeutics, Montpellier, France. emmanuel.bourinet@igf.cnrs.fr.
11
Inserm U-1191, Montpellier, France. emmanuel.bourinet@igf.cnrs.fr.
12
CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France. emmanuel.bourinet@igf.cnrs.fr.
13
Université Montpellier, Montpellier, France. emmanuel.bourinet@igf.cnrs.fr.
14
Laboratories of Excellence - Ion Channel Science and Therapeutics, Montpellier, France. pierre-francois.mery@igf.cnrs.fr.
15
Inserm U-1191, Montpellier, France. pierre-francois.mery@igf.cnrs.fr.
16
CNRS UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France. pierre-francois.mery@igf.cnrs.fr.
17
Université Montpellier, Montpellier, France. pierre-francois.mery@igf.cnrs.fr.

Abstract

The T-type calcium channel, Cav3.2, is necessary for acute pain perception, as well as mechanical and cold allodynia in mice. Being found throughout sensory pathways, from excitatory primary afferent neurons up to pain matrix structures, it is a promising target for analgesics. In our study, Cav3.2 was detected in ~60% of the lamina II (LII) neurons of the spinal cord, a site for integration of sensory processing. It was co-expressed with Tlx3 and Pax2, markers of excitatory and inhibitory interneurons, as well as nNOS, calretinin, calbindin, PKCγ and not parvalbumin. Non-selective T-type channel blockers slowed the inhibitory but not the excitatory transmission in LII neurons. Furthermore, T-type channel blockers modified the intrinsic properties of LII neurons, abolishing low-threshold activated currents, rebound depolarizations, and blunting excitability. The recording of Cav3.2-positive LII neurons, after intraspinal injection of AAV-DJ-Cav3.2-mcherry, showed that their intrinsic properties resembled those of the global population. However, Cav3.2 ablation in the dorsal horn of Cav3.2GFP-Flox KI mice after intraspinal injection of AAV-DJ-Cav3.2-Cre-IRES-mcherry, had drastic effects. Indeed, it (1) blunted the likelihood of transient firing patterns; (2) blunted the likelihood and the amplitude of rebound depolarizations, (3) eliminated action potential pairing, and (4) remodeled the kinetics of the action potentials. In contrast, the properties of Cav3.2-positive neurons were only marginally modified in Cav3.1 knockout mice. Overall, in addition to their previously established roles in the superficial spinal cord and in primary afferent neurons, Cav3.2 channel appear to be necessary for specific, significant and multiple controls of LII neuron excitability.

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