부산대학교 도서관

• Ca V 3 channel location is altered in L4 adjacent intact afferent fibers after L5-6 SNL. • Ca V 3.2 channel distribution changes by concentrating on the neuronal soma. • T- and N-type channels in L3-4 sensory neurons are targets of Cdk5. • Ca V 3 channel phosphorylation by Cdk5 may contribute to nerve injury-induced allodynia. Voltage-gated Ca2+ (Ca V) channels regulate multiple cell processes, including neurotransmitter release, and have been associated with several pathological conditions, such as neuropathic pain. Cdk5, a neuron-specific kinase, may phosphorylate Ca V channels, altering their functional expression. During peripheral nerve injury, upregulation of Ca V channels and Cdk5 in the dorsal root ganglia (DRG) and the spinal cord, has been correlated with allodynia. We recently reported an increase in the amplitude of the C component of the compound action potential (cAP) of afferent fibers in animals with allodynia induced by L5-6 spinal nerve ligation (SNL), recorded in the corresponding dorsal roots. This was related to an increase in T-type (Ca V 3.2) channels generated by Cdk5-mediated phosphorylation. Here, we show that Ca V channel functional expression is also altered in the L4 adjacent intact afferent fibers in rats with allodynia induced by L5-6 SNL. Western blot analysis showed that both Cdk5 and Ca V 3.2 total levels are not increased in the DRG L3-4, but their subcellular distribution changes by concentrating on the neuronal soma. Likewise, the Cdk5 inhibitor olomoucine affected the rapid and the slow C components of the cAP recorded in the dorsal roots. Patch-clamp recordings revealed an increase in T- and N-type currents recorded in the soma of acute isolated L3-4 sensory neurons after L5-6 SNL, which was prevented by olomoucine. These findings suggest changes in Ca V channels location and function in L3-4 afferent fibers associated with Cdk5-mediated phosphorylation after L5-6 SNL, which may contribute to nerve injury-induced allodynia. [ABSTRACT FROM AUTHOR]