However, the precise regulation of Kv4 in the development of epilepsy and its underlying mechanism remain unclear. In this study, we investigated whether the expression of the Kv4.2 channel and of its major modulator, voltage-dependent potassium channel-interacting protein this website (KChIP1), is altered following lithium-pilocarpine induced status epilepticus (SE) and the chronic-epilepsy phase in the rat model. We found that Kv4.2 and KChIP1 expression was transiently up-regulated following SE, whereas it was down-regulated during the chronic phase: this was most prominent in the CA1 and CA3 regions. The time-course analysis of the protein expression level showed that

the peak Kv4.2 up-regulation was between 6 and 24 h after SE, whereas KChIP1 expression was increased earlier and for a shorter period. The temporospatial changes in Kv4.2 were very similar to those

of its major modulator KChIP1. We compared the difference in 4-aminopyridine (4-AP)-induced intracellular calcium ([Ca(2+)]i) elevation between model and control brain slices. The results showed that the [Ca(2+)]i elevation induced by the Kv4 channel blocker 4-AP was aggravated and prolonged in the model slice after SE. The functional relevance of these changes in Ca(2+) homeostasis and Kv4.2 and KChIP1 expression may be associated with intrinsic neuronal excitability regulation and epileptogenesis. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Episodic ataxia type 1 (EA1) is a rare human neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by abrupt movements, emotional stress and fatigue. An Italian family has ICG-001 in vivo been identified where related members displayed continuous myokymia, episodes of ataxia, attacks characterized by myokymia only, and neuromyotonia. A novel missense mutation (F414C), in the C-terminal region of the K(+) channel Kv1.1, was identified in the affected individuals. The mutant homotetrameric channels were non-functional in Xenopus laevis oocytes. In addition, heteromeric channels resulting from the co-expression of wild-type Kv1.1 and Kv1.1(F414C), or wild-type Kv1.2 and Kv1.1(F414C) subunits

buy eFT-508 displayed reduced current amplitudes and altered gating properties. This indicates that the pathogenic effect of this KCNA1 mutation is likely to be related to the defective functional properties we have identified. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“DYT1 is the most common inherited dystonia, a neurological syndrome that causes disabling involuntary muscle contractions. This autosomal dominant disease is caused by a glutamic acid deletion near the carboxy-terminus in the protein torsinA. Cell- and animal-based studies have shown how the DYT1 mutation causes mutant torsinA to redistribute from the endoplasmic reticulum to the nuclear envelope, acting through a dominant negative effect over the wild type protein.