Cdk5-Dependent Phosphorylation of CaV3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers.

摘要: Voltage-gated T-type Ca2+ (CaV3) channels regulate diverse physiological events, including neuronal excitability, and have been linked to several pathological conditions such as absence epilepsy, cardiovascular diseases, neuropathic pain. It is also acknowledged that calcium/calmodulin-dependent protein kinase II kinases A C the activity of channels. Interestingly, peripheral nerve injury induces tactile allodynia upregulates CaV3.2 cyclin-dependent 5 (Cdk5) in dorsal root ganglia (DRG) spinal horn. Here, we report recombinant expressed HEK293 cells are regulatory targets Cdk5. Site-directed mutagenesis showed relevant sites for this regulation residues S561 S1987. We found Cdk5 may channel functional expression rats with mechanical induced by ligation (SNL). Consequently, inhibitor olomoucine affected compound action potential recorded nerves, well paw withdrawal threshold. Likewise, was upregulated after SNL DRG. These findings unveil a novel mechanism how phosphorylation suggest increased Cdk5-mediated contributes injury-induced allodynia.SIGNIFICANCE STATEMENT Neuropathic pain current public health challenge. can develop result or illness. various ion be altered pain, sensory neurons, where they play role cellular excitability. The present work shows exacerbated preclinical model increases This finding understanding molecular pathophysiology disease. Additionally, substantial translational impact, since it describes pathway could represent an interesting therapeutic alternative