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

作者：Miriam Candelas, Ana Reynders, Margarita Arango-Lievano, Christoph Neumayer, Antoine Fruquière, Elsa Demes, Jawed Hamid, Céline Lemmers, Claire Bernat, Arnaud Monteil, Vincent Compan, Sophie Laffray, Perrine Inquimbert, Yves Le Feuvre, Gerald W. Zamponi, Aziz Moqrich, Emmanuel Bourinet, Pierre‐François Méry · 发表于：Scientific Reports · 年份：2019 · DOI：10.1038/s41598-019-39703-3 · 被引用次数：57 · 研究领域：Ion channel regulation and function、Pain Mechanisms and Treatments、Neuroscience and Neural Engineering

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 Cav3.2 GFP-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-positiv...