A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy

0511368 - ÚOCHB 2020 RIV US eng J - Článek v odborném periodiku
Gaifullina, Aisylu S. - Lazniewska, Joanna - Gerasimova, E. V. - Burkhanova, G. F. - Rzhepetskyy, Yuriy - Tomin, Andriy - Rivas-Ramirez, Paula - Huang, J. - Cmarko, Leoš - Zamponi, G. W. - Sitdikova, G. F. - Weiss, Norbert
A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy.
Pain. Roč. 160, č. 12 (2019), s. 2798-2810. ISSN 0304-3959. E-ISSN 1872-6623
Institucionální podpora: RVO:61388963
Klíčová slova: homocysteinemia * homocysteine * pain * allodynia * calcium channel * T-type channel * Cav3.2
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.483, rok: 2019
Způsob publikování: Omezený přístup
https://journals.lww.com/pain/Abstract/2019/12000/A_potential_role_for_T_type_calcium_channels_in.13.aspx

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.
Trvalý link: http://hdl.handle.net/11104/0301651