Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy.
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.
Shin
Minyoung
M
Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwest University Medical School, Chicago, IL 60611-3008, USA.
Brager
Darrin
D
Jaramillo
Thomas C
TC
Johnston
Daniel
D
Chetkovich
Dane M
DM
D000818:Animals; D053447:Channelopathies / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism* / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C523657:Pex5l protein, rat; D015221:Potassium Channels; D021122:Protein Subunits