• Aisylu S Gaifullina, Joanna Lazniewska, Elena V Gerasimova, Gulshat F Burkhanova, Yuriy Rzhepetskyy, Andriy Tomin, Paula Rivas-Ramirez, Junting Huang, Leos Cmarko, Gerald W Zamponi, Guzel F Sitdikova, and Norbert Weiss.
• Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic.
• Pain. 2019 Dec 1; 160 (12): 2798-2810.

AbstractHomocysteinemia 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.

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