The WEISS Lab


Pathophysiology of Ion Channels

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


Journal article


Aisylu S Gaifullina, J. Lazniewska, E. Gerasimova, Gulshat Burkhanova, Y. Rzhepetskyy, A. Tomin, P. Rivas-Ramírez, Junting Huang, Leos Cmarko, G. Zamponi, G. Sitdikova, N. Weiss
Pain, 2019

Semantic Scholar DOI PubMed Video abstract
Cite

Cite

APA
Gaifullina, A. S., Lazniewska, J., Gerasimova, E., Burkhanova, G., Rzhepetskyy, Y., Tomin, A., … Weiss, N. (2019). A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy. Pain.

Chicago/Turabian
Gaifullina, Aisylu S, J. Lazniewska, E. Gerasimova, Gulshat Burkhanova, Y. Rzhepetskyy, A. Tomin, P. Rivas-Ramírez, et al. “A Potential Role for T-Type Calcium Channels in Homocysteinemia-Induced Peripheral Neuropathy.” Pain (2019).

MLA
Gaifullina, Aisylu S., et al. “A Potential Role for T-Type Calcium Channels in Homocysteinemia-Induced Peripheral Neuropathy.” Pain, 2019.


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 upon 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 via a PKC-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.