Immunohistochemical localization of DPP10 in rat brain supports the existence of a Kv4/KChIP/DPPL ternary complex in neurons

J Comp Neurol. 2015 Mar 1;523(4):608-28. doi: 10.1002/cne.23698. Epub 2014 Dec 19.

Abstract

Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown. In this study, we generated a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. Absent from glia, DPP10 proteins appear mainly in the cell bodies of DPP10(+) neurons, not only at the plasma membrane but also in the cytoplasm. At least 6.4% of inhibitory interneurons in the hippocampus coexpressed Kv4.3, KChIP1, and DPP10, with the highest density in the CA1 strata alveus/oriens/pyramidale and the dentate hilus. Colocalization of Kv4.3/KChIP1/DPP10 was also detected in at least 6.9% of inhibitory interneurons scattered throughout the neocortex. Both hippocampal and neocortical Kv4.3/KChIP1/DPP10(+) inhibitory interneurons expressed parvalbumin or somatostatin, but not calbindin or calretinin. Furthermore, we found colocalization of Kv4.2/Kv4.3/KChIP3/DPP10 in neocortical layer 5 pyramidal neurons and olfactory bulb mitral cells. Together, although DPP10 is also expressed in some brain neurons lacking Kv4 (such as parvalbumin- and somatostatin-positive Golgi cells in the cerebellum), colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo.

Keywords: KChIP1; KChIP3; Kv4.2; Kv4.3; subthreshold A-type K+ currents; voltage-gated K+ channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Kv Channel-Interacting Proteins / metabolism*
  • Male
  • Microscopy, Confocal
  • Neurons / metabolism*
  • Rats, Sprague-Dawley
  • Shal Potassium Channels / metabolism*
  • Transfection

Substances

  • Kv Channel-Interacting Proteins
  • Shal Potassium Channels
  • DPP10 protein, rat
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases