Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10 (DPP10)

Biophys J. 2004 Oct;87(4):2380-96. doi: 10.1529/biophysj.104.042358.


The dipeptidyl aminopeptidase-like protein DPPX (DPP6) associates with Kv4 potassium channels, increasing surface trafficking and reconstituting native neuronal ISA-like properties. Dipeptidyl peptidase 10 (DPP10) shares with DPP6 a high amino acid identity, lack of enzymatic activity, and expression predominantly in the brain. We used a two-electrode voltage-clamp and oocyte expression system to determine if DPP10 also interacts with Kv4 channels and modulates their expression and function. Kv4.2 coimmunoprecipitated with HA/DPP10 from extracts of oocytes heterologously expressing both proteins. Coexpression with DPP10 and HA/DPP10 enhanced Kv4.2 current by approximately fivefold without increasing protein level. DPP10 also remodeled Kv4.2 kinetic and steady-state properties by accelerating time courses of inactivation and recovery (taurec: WT = 200 ms, +DPP10 = 78 ms). Furthermore, DPP10 introduced hyperpolarizing shifts in the conductance-voltage relationship (approximately 19 mV) as well as steady-state inactivation (approximately 7 mV). The effects of DPP10 on Kv4.1 were similar to Kv4.2; however, distinct biophysical differences were observed. Additional experiments suggested that the cytoplasmic N-terminal domain of DPP10 determines the acceleration of inactivation. In summary, DPP10 is a potent modulator of Kv4 expression and biophysical properties and may be a critical component of somatodendritic ISA channels in the brain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Cell Membrane / physiology*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
  • Gene Expression Regulation / physiology*
  • Humans
  • Ion Channel Gating / physiology*
  • Membrane Potentials / physiology*
  • Oocytes / physiology*
  • Potassium Channels, Voltage-Gated / physiology*
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Shal Potassium Channels
  • Xenopus laevis


  • KCND1 protein, human
  • KCND2 protein, human
  • Potassium Channels, Voltage-Gated
  • Recombinant Proteins
  • Shal Potassium Channels
  • DPP10 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases