Coexpression of auxiliary subunits KChIP and DPPL in potassium channel Kv4-positive nociceptors and pain-modulating spinal interneurons

摘要

Subthreshold A-type K+ currents (I(SA)s) have been recorded from the somata of nociceptors and spinal lamina II excitatory interneurons, which sense and modulate pain, respectively. Kv4 channels are responsible for the somatodendritic I(SA)s. Accumulative evidence suggests that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits and two types of auxiliary subunits: K+ channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPPLs). Previous reports have shown Kv4.3 in a subset of nonpeptidergic nociceptors and Kv4.2/Kv4.3 in certain spinal lamina II excitatory interneurons. However, whether and which KChIP and DPPL are coexpressed with Kv4 in these I-SA-expressing pain-related neurons is unknown. In this study we mapped the protein distribution of KChIP1, KChIP2, KChIP3, DPP6, and DPP10 in adult rat dorsal root ganglion (DRG) and spinal cord by immunohistochemistry. In the DRG, we found colocalization of KChIP1, KChIP2, and DPP10 in the somatic surface and cytoplasm of Kv4.3(+) nociceptors. KChIP3 appears in most A and A sensory neurons as well as a small population of peptidergic nociceptors, whereas DPP6 is absent in sensory neurons. In the spinal cord, KChIP1 is coexpressed with Kv4.3 in the cell bodies of a subset of lamina II excitatory interneurons, while KChIP1, KChIP2, and DPP6 are colocalized with Kv4.2 and Kv4.3 in their dendrites. Within the dorsal horn, besides KChIP3 in the inner lamina II and lamina III, we detected DPP10 in most projection neurons, which transmit pain signal to brain. The results suggest the existence of Kv4/KChIP/DPPL ternary complexes in I-SA-expressing nociceptors and pain-modulating spinal interneurons. J. Comp. Neurol. 524:846-873, 2016. (c) 2015 Wiley Periodicals, Inc.