Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability.
Febrile seizures are the most common type of developmental seizures, affecting up to 5% of children. Experimental complex febrile seizures involving the immature rat hippocampus led to a persistent lowering of seizure threshold despite an upregulation of inhibition. Here we provide a mechanistic resolution to this paradox by showing that, in the hippocampus of rats that had febrile seizures, the long-lasting enhancement of the widely expressed intrinsic membrane conductance Ih converts the potentiated synaptic inhibition to hyperexcitability in a frequency-dependent manner. The altered gain of this molecular inhibition-excitation converter reveals a new mechanism for controlling the balance of excitation-inhibition in the limbic system. In addition, here we show for the first time that h-channels are modified in a human neurological disease paradigm.
Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, California, USA.
K
K
Chen
I
I
Aradi
N
N
Thon
M
M
Eghbal-Ahmadi
T Z
TZ
Baram
I
I
Soltesz
D000818:Animals; D003198:Computer Simulation; D006624:Hippocampus / Q000503:physiopathology*; D008564:Membrane Potentials; D051381:Rats; D017207:Rats, Sprague-Dawley; D003294:Seizures, Febrile / Q000503:physiopathology*