TY - JOUR
T1 - Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy
AU - Shin, Minyoung
AU - Brager, Darrin
AU - Jaramillo, Thomas C.
AU - Johnston, Daniel
AU - Chetkovich, Dane M.
N1 - Funding Information:
We thank Alan Lewis, and Won Jun Choi for comments on the manuscript, and Jim Chen, Daniel E. Choi, Felix L. Nunez Santana, Eric Naylor, Ayman Gheith and Jennifer Stern for technical assistance with immunohistochemistry and EEG recording, Dr. Rishikesh Narayanan for assistance with the analysis of cell resonance and Dr. Raymond Chitwood for technical help with the analysis software. This research was supported by grants from the National Institutes of Health (R21 NS052595 to DC) and (MH48432, MH44754, NS37444 to D.J), and from the Partnership for Pediatric Epilepsy Research, which includes the American Epilepsy Society, the Epilepsy Foundation, The Epilepsy Project, Fight Against Childhood Epilepsy and Seizures (f.a.c.e.s.), and Parents Against Childhood Epilepsy (P.A.C.E.).
PY - 2008/10
Y1 - 2008/10
N2 - 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. Ih, 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.
AB - 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. Ih, 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.
KW - Epilepsy
KW - Hyperpolarization-activated cyclic
KW - Kainic acid
KW - Nucleotide-gated channel
KW - Seizure
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U2 - 10.1016/j.nbd.2008.06.013
DO - 10.1016/j.nbd.2008.06.013
M3 - Article
C2 - 18657617
AN - SCOPUS:51349110413
SN - 0969-9961
VL - 32
SP - 26
EP - 36
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -