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

作者：Shin Minyoung; Brager Darrin; Jaramillo Thomas C; Johnston Daniel; Chetkovich Dane M^*

来源：Neurobiology of Disease, 2008, 32(1): 26-36.

DOI：10.1016/j.nbd.2008.06.013

• epilepsy
• seizure
• hyperpolarization-activated cyclic
• nucleotide-gated channel
• kainic acid

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-after 30 d following SE, 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.

• 出版日期2008-10
• 单位西北大学