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CO2 chemoreception may be related to modulation of inward rectifier K+ channels (Kir channels) in brainstem neurons. Kir4.1 is expressed predominantly in the brainstem and inhibited during hypercapnia. Although the homomeric Kir4.1 only responds to severe intracellular acidification, coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivities(More)
With a worldwide incidence as high as 6.7% of children, febrile seizures are one of the most common reasons for seeking pediatric care, but the mechanisms underlying generation of febrile seizures are poorly understood. Febrile seizures have been suspected to have a genetic basis, and recently, mutations in GABAA receptor and sodium channel genes have been(More)
Activation of protein kinase A (PKA) increases Na+ current derived from the human cardiac Na+ channel, hH1, in a slow, nonsaturable manner. This effect is prevented by compounds that disrupt plasma membrane recycling, implying enhanced trafficking of channels to the cell membrane as the mechanism responsible for Na+ current potentiation. To investigate the(More)
The GABA(A) receptor gamma2 subunit mutation, Q351X, associated with generalized epilepsy with febrile seizures plus (GEFS+), created a loss of function with homozygous expression. However, heterozygous gamma2(+/-) gene deletion mice are seizure free, suggesting that the loss of one GABRG2 allele alone in heterozygous patients may not be sufficient to(More)
OBJECTIVE Genetic epilepsies and many other human genetic diseases display phenotypic heterogeneity, often for unknown reasons. Disease severity associated with nonsense mutations is dependent partially on mutation gene location and resulting efficiency of nonsense-mediated mRNA decay (NMD) to eliminate potentially toxic proteins. Nonsense mutations in the(More)
The GABA(A) receptor γ2 subunit nonsense mutation Q351X has been associated with the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus, which includes a spectrum of seizures types from febrile seizures to Dravet syndrome. Although most genetic epilepsy syndromes are mild and remit with age, Dravet syndrome has a more severe clinical(More)
Approximately one-third of human genetic diseases are caused by premature translation-termination codon (PTC)-generating mutations. These mutations in sodium channel and GABA(A) receptor genes have been associated with idiopathic generalized epilepsies, but the cellular consequences of the PTCs on the mutant channel subunit biogenesis and function are(More)
Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In(More)
Genetic epilepsy and neurodegenerative diseases are two common neurological disorders that are conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies who have impaired development and often go on to die of their disease respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets.(More)
Emerging evidence shows that glioblastoma multiforme (GBM) originates from cancer stem cells (CSCs). Characterization of CSC-specific signalling pathways would help identify new therapeutic targets and perhaps lead to the development of more efficient therapies selectively targeting CSCs. Here; we successfully dedifferentiated two patient-derived GBM cell(More)