A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels

Neurosci Lett. 2009 Jan 16;449(3):189-94. doi: 10.1016/j.neulet.2008.10.098. Epub 2008 Nov 5.


The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Line, Transformed
  • Cloning, Molecular / methods
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Humans
  • Kinetics
  • Kv Channel-Interacting Proteins / genetics
  • Kv Channel-Interacting Proteins / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / classification
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Peptide Hydrolases / genetics*
  • Peptide Hydrolases / metabolism
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Shal Potassium Channels / genetics
  • Shal Potassium Channels / metabolism*
  • Transfection / methods


  • Kv Channel-Interacting Proteins
  • Nerve Tissue Proteins
  • Potassium Channels
  • Protein Isoforms
  • RNA, Messenger
  • Shal Potassium Channels
  • Green Fluorescent Proteins
  • DPP6 protein, human
  • Peptide Hydrolases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases