Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy

Neurobiol Dis. 2008 Oct;32(1):26-36. doi: 10.1016/j.nbd.2008.06.013. Epub 2008 Jul 3.


Many animal models of temporal lobe epilepsy (TLE) begin with status epilepticus (SE) followed by a latency period. Increased hippocampal pyramidal neuron excitability may contribute to seizures in TLE. I(h), mediated by h channels, regulates intrinsic membrane excitability by modulating synaptic integration and dampening dendritic calcium signaling. In a rat model of TLE, we found bidirectional changes in h channel function in CA1 pyramidal neurons. 1-2 d after SE, before onset of spontaneous seizures, physiological parameters dependent upon h channels were augmented and h channel subunit surface expression was increased. 28-30 d following SE, after onset of spontaneous seizures, h channel function in dendrites was reduced, coupled with diminished h channel subunit surface expression and relocalization of subunits from distal dendrites to soma. These results implicate h channel localization as a molecular mechanism influencing CA1 excitability in TLE.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Channelopathies / metabolism*
  • Channelopathies / pathology*
  • Channelopathies / physiopathology
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Cyclic Nucleotide-Gated Cation Channels / physiology
  • Epilepsy, Temporal Lobe / metabolism*
  • Epilepsy, Temporal Lobe / pathology*
  • Epilepsy, Temporal Lobe / physiopathology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Male
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology
  • Protein Subunits / metabolism*
  • Protein Subunits / physiology
  • Protein Transport / genetics
  • Rats
  • Rats, Sprague-Dawley


  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Pex5l protein, rat
  • Potassium Channels
  • Protein Subunits