| Summary: | 碩士 === 國立陽明大學 === 神經科學研究所 === 100 === Kv4 channels evoke A-type K+ currents which play a critical role in regulating neuronal excitability. Native Kv4 channels function in complex comprising Kv4 α-subunits and accessory β-subunits, such as cytosolic K+ channel interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase like proteins (DPPLs). Compared with Kv4 α-subunits alone, A-type K+ currents are robustly increased when they are co-expressed with accessory β-subunits in heterologous systems. The protein expression of Kv4 α- or β- subunits affect protein levels of the other. However, the related physiological significance has not been explored. Kv4.3, one of the Kv4 α-subunits, is expressed selectively in the cell bodies of a subset of pain-sensing neurons and its down-regulation induces mechanical pain. In this study, we found that KChIP1 and Kv4.3 were co-expressed in a subset of pain-sensing neurons. In a neuropathic pain model induced by lumbar spinal nerve ligation in the rat, the protein level of KChIP1 was reduced in pain-sensing neurons, same as that of Kv4.3. After knockdown either KChIP1 or Kv4.3 expression by intrathecal injection of gene-specific antisense oligonucleotide, KChIP1 and Kv4.3 protein levels were simultaneously decreased in pain-sensing neurons and mechanical hypersensitivity was induced. We also examined that knockdown effect of another Kv4 β-subunit DPP10, whose mRNA has been detected in the DRG. Our data showed that mechanical hypersensitivity was induced although Kv4.3 protein level was not affected. These data reveal that after decreasing either KChIP1 or DPP10 β-subunit in the DRG, mechanical pain develops. Kv4.3 and KChIP1 protein levels are co-dependent, whereas DPP10 and Kv4.3 protein levels are not.
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