A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy
Date
2019
Authors
Gaifullina, A.S.
Lazniewska, J.
Gerasimova, E.V.
Burkhanova, G.F.
Rzhepetskyy, Y.
Tomin, A.
Rivas Ramirez, P.
Huang, J.
Cmarko, L.
Zamponi, G.W.
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Journal article
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Pain, 2019; 160(2):2798-2810
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Abstract
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.
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Copyright 2019 International Association for the Study of Pain