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

Shin M, Brager D, Jaramillo TC, Johnston D, Chetkovich DM
Neurobiol Dis. 2008 32 (1): 26-36

PMID: 18657617 · PMCID: PMC2626192 · DOI:10.1016/j.nbd.2008.06.013

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.

MeSH Terms (14)

Animals Channelopathies Cyclic Nucleotide-Gated Cation Channels Epilepsy, Temporal Lobe Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Male Membrane Proteins Mice Nerve Tissue Proteins Potassium Channels Protein Subunits Protein Transport Rats Rats, Sprague-Dawley

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