Cav3.2 T-type calcium channels control acute itch in mice

Vinicius M. Gadotti; Joanna M. Kreitinger; Nicholas B. Wageling; Dylan Budke; Philippe Diaz; Gerald W. Zamponi

doi:10.1186/s13041-020-00663-9

Cav3.2 T-type calcium channels control acute itch in mice

Vinicius M. Gadotti
, Joanna M. Kreitinger
, Nicholas B. Wageling
, Dylan Budke
, Philippe Diaz
, Gerald W. Zamponi

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Cav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated the effect of the T-type calcium channel blocker DX332 in male and female wild-type mice injected with either histamine or chloroquine. Cav3.2 null mice exhibited decreased scratching responses during both histamine- and chloroquine-induced acute itch. DX332 co-injected with the pruritogens inhibited scratching responses of male and female mice treated with either histamine or chloroquine. Altogether, our data provide strong evidence that Cav3.2 T-type channels exert an important role in modulating histamine-dependent and -independent itch transmission in the primary sensory afferent pathway, and highlight these channels as potential pharmacological targets to treat pruritus.

Original language	English
Article number	119
Journal	Molecular Brain
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13041-020-00663-9
State	Published - Sep 1 2020

Funding

This work was supported by a Foundation Grant from the Canadian Institutes of Health Research, and a grant from Alberta Innovates to GWZ. GWZ is a Canada Research Chair. VG is supported by the Vi Riddell program in Pediatric Pain. This work was also supported by the by the National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health: 1R43AR076842–01 and 1R41NS105304–01 (P.D., JMK, NBW), P20GM103546 (P.D.). The content of this paper is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Funders	Funder number
P20GM103546, 1R41NS105304–01
R43AR076842
Canadian Institutes of Health Research
Alberta Innovates

Keywords

Cav3.2 T-type channel
Chloroquine
Histamine
Itch
Pruritus

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10.1186/s13041-020-00663-9

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title = "Cav3.2 T-type calcium channels control acute itch in mice",

abstract = "Cav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated the effect of the T-type calcium channel blocker DX332 in male and female wild-type mice injected with either histamine or chloroquine. Cav3.2 null mice exhibited decreased scratching responses during both histamine- and chloroquine-induced acute itch. DX332 co-injected with the pruritogens inhibited scratching responses of male and female mice treated with either histamine or chloroquine. Altogether, our data provide strong evidence that Cav3.2 T-type channels exert an important role in modulating histamine-dependent and -independent itch transmission in the primary sensory afferent pathway, and highlight these channels as potential pharmacological targets to treat pruritus.",

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AU - Kreitinger, Joanna M.

AU - Wageling, Nicholas B.

AU - Budke, Dylan

AU - Diaz, Philippe

AU - Zamponi, Gerald W.

PY - 2020/9/1

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Cav3.2 T-type calcium channels control acute itch in mice

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