Epilepsy may result from abnormal function of ion channels, such as those caused by genetic mutations. Recently, pathological alterations of the expression or localization of normal channels have been implicated in epilepsy generation, and termed 'acquired channelopathies'. Altered expression levels of the HCN channels - that conduct the hyperpolarization-activated current, I(h) - have been demonstrated in hippocampus of patients with severe temporal lobe epilepsy as well as in animal models of temporal lobe and absence epilepsies. Here we probe the mechanisms for the altered expression of HCN channels which is provoked by seizures. In organotypic hippocampal slice cultures, seizure-like events selectively reduced HCN type 1 channel expression and increased HCN2 mRNA levels, as occurs in vivo. The mechanisms for HCN1 reduction involved Ca(2+)-permeable AMPA receptor-mediated Ca(2+) influx, and subsequent activation of Ca(2+)/calmodulin-dependent protein kinase II. In contrast, upregulation of HCN2 expression was independent of these processes. The data demonstrate an orchestrated program for seizure-evoked transcriptional channelopathy involving the HCN channels that may contribute to certain epilepsies.

S and full research articles published in SLEEP, the official journal of the APSS. Sleep and sleep disorder scientific findings.

Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic terminals, glutamate binds to both ionotropic and metabotropic receptors to mediate fast, slow, and persistent effects on synaptic transmission and integrity. There are three types of ionotropic glutamate receptors. N-Methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors are principally activated by the agonist bearing its name and are permeable to cationic flux; hence, their activation results in membrane depolarization. All ionotropic glutamate receptors are believed to be composed of four distinct subunits, each of which is topologically arranged with three transmembrane-spanning and one pore-lining (hairpin loop) domain. In contrast, metabotropic glutamate receptors are G protein (guanine nucleotide-binding protein) -coupled receptors linked to second-messenger systems. Group I metabotropic glutamate receptors are linked to phospholipase C, which results in phosphoinositide hydrolysis and release of calcium from intracellular stores. Group II and group III metabotropic glutamate receptors are negatively linked to adenylate cyclase, which catalyzes the production of cyclic adenosine monophosphate. Each metabotropic glutamate receptor is composed of seven transmembrane-spanning domains, similar to other members of the superfamily of metabotropic receptors, which includes noradrenergic, muscarinic acetylcholinergic, dopaminergic, serotonergic (except type 3 receptors), and γ-aminobutyric acid (GABA) type B receptors. This review summarizes the relevant molecular biology and ontogeny of glutamate receptors in the central nervous system and highlights some of the roles that they can play during brain development and in certain disease states. (J Child Neurol 2004;19:343-360).