Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the epileptogenic agent pentylenetetrazol on eight cloned voltage-operated mammalian potassium channels (expressed in oocytes of Xenopus laevis) was investigated in order to contribute to an explanation for the brain area-specific differences in seizure susceptibility. Pentylenetetrazol increased the potassium currents at more negative and decreased them at more positive potentials for the channels of the Kv1 gene family, whereas for the other channels the currents were decreased over the whole potential range. The sensitivities of the different potassium channels to the epileptogenic agent were different. At a potential of 0 mV, for example, there were strong reductions for the Kv1.1, Kv1.4 and Kv2.1 currents, whereas the decrease was smaller for the Kv1.3 and Kv1.6 currents and was negligible for the Kv1.2, Kv1.5 and Kv3.4 currents. Correlating these data with the distribution patterns of the potassium channels in the hippocampus, the neocortex and the cerebellum (representing examples of brain areas of distinct seizure susceptibility) revealed that in brain areas with higher seizure susceptibility the overall sensitivity of the potassium channels to the epileptogenic agent is augmented. As a whole, the findings give the first evidence that the differences in distributions and properties of potassium channels contribute to differences in the seizure susceptibility of brain areas.
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PMID:Diversity of potassium channels contributing to differences in brain area-specific seizure susceptibility: sensitivity of different potassium channels to the epileptogenic agent pentylenetetrazol. 905 58

Using assay-directed fractionation of the venom from the vermivorous cone snail Conus planorbis, we isolated a new conotoxin, designated pl14a, with potent activity at both nicotinic acetylcholine receptors and a voltage-gated potassium channel subtype. pl14a contains 25 amino acid residues with an amidated C-terminus, an elongated N-terminal tail (six residues), and two disulfide bonds (1-3, 2-4 connectivity) in a novel framework distinct from other conotoxins. The peptide was chemically synthesized, and its three-dimensional structure was demonstrated to be well-defined, with an alpha-helix and two 3(10)-helices present. Analysis of a cDNA clone encoding the prepropeptide precursor of pl14a revealed a novel signal sequence, indicating that pl14a belongs to a new gene superfamily, the J-conotoxin superfamily. Five additional peptides in the J-superfamily were identified. Intracranial injection of pl14a in mice elicited excitatory symptoms that included shaking, rapid circling, barrel rolling, and seizures. Using the oocyte heterologous expression system, pl14a was shown to inhibit both a K+ channel subtype (Kv1.6, IC50 = 1.59 microM) and neuronal (IC50 = 8.7 microM for alpha3beta4) and neuromuscular (IC50 = 0.54 microM for alpha1beta1 epsilondelta) subtypes of the nicotinic acetylcholine receptor (nAChR). Similarities in sequence and structure are apparent between the middle loop of pl14a and the second loop of a number of alpha-conotoxins. This is the first conotoxin shown to affect the activity of both voltage-gated and ligand-gated ion channels.
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PMID:A novel conotoxin inhibitor of Kv1.6 channel and nAChR subtypes defines a new superfamily of conotoxins. 1681 32

Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, associated with well described spontaneous electromyographic features. It is usually an acquired disorder associated with autoantibodies against neuronal voltage-gated potassium channels. However, mutations of KCNA1, encoding the K(+) channel subunit hKv1.1, have been reported in rare families with neuromyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal seizures and myokymia. We report a three-generation family with inherited neuromyotonia without evidence of immunological involvement. Genetic study excluded mutations in KCNA1, KCNA2, KCNA6 and KCNQ2 genes. Our study does not completely exclude the involvement of other genes encoding ion channels subunits in the pathogenesis of this disorder. Further studies of familial cases will shed light on the molecular basis of inherited neuromyotonia.
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PMID:Inherited neuromyotonia: a clinical and genetic study of a family. 1714 Jul 92

In order to confirm the species-specific distribution of voltage-gated K(+) (Kv) channels and the definitive relationship between their immunoreactivities and seizure activity, we investigated Kv1 channel immunoreactivities in the hippocampus of seizure resistant (SR) and seizure sensitive (SS) gerbils. There was distinct difference of the Kv1 channel subtypes immunoreactivity in the hippocampi in both SR and SS gerbils. Kv1.1, Kv1.2, Kv1.3, Kv1.4, and Kv1.6 immunoreactivities in the SS gerbil hippocampus were lower than that in the SR gerbil hippocampus. However, Kv1 immunoreactivities were obviously presented in astrocyte within the stratum radiatum of the CA1 region of pre-seizure SS gerbil hippocampus. Following seizure-onset, Kv1 immunoreactivities (except Kv1.5) were markedly elevated, whereas their immunoreactivites in astrocytes were down-regulated. Therefore, the present study demonstrates that seizure activity may distinctly affect neuroglial Kv1 immunoreactivities in the gerbil hippocampus.
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PMID:Seizure activity affects neuroglial Kv1 channel immunoreactivities in the gerbil hippocampus. 1739 9

In order to confirm the species-specific distribution of voltage-gated K(+) (Kv) channels and the definitive relationship between their immunoreactivities and seizure activity, we investigated Kv2.x, Kv3.x and Kv4.x channel immunoreactivities in the hippocampi of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference in Kv2.1, Kv3.4, Kv4.2 and Kv4.3 immunoreactivity in the hippocampus between SR and SS gerbils. In comparison to SR gerbils, Kv3.1b immunoreactivity in neurons was significantly lower in SS gerbils instead Kv3.1b-immunoreactive astrocytes were clearly observed in SS gerbils (p<0.05). Kv3.2 immunoreactivity was also significantly lower in neurons of SS gerbils than in those of SR gerbils (p<0.05). Considering the findings of our previous study, these findings suggest that delayed rectifier K(+) channels (Kv1.1, Kv1.2, Kv1.5, Kv1.6, Kv2.1 and Kv3.1-2), not A-type K(+) channels (Kv1.4, Kv3.4 and Kv4.x), may be down-regulated in the SS gerbil hippocampus, as compared to SR gerbils.
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PMID:Down-regulation of delayed rectifier K+ channels in the hippocampus of seizure sensitive gerbils. 1966 28

Interneuronal functional diversity is thought to be an important factor in the control of neural network oscillations in many brain regions. Specifically, interneuron action potential firing patterns are thought to modulate brain rhythms. In neurological disorders such as epilepsy where brain rhythms are significantly disturbed interneuron function is largely unexplored. Thus the purpose of this study was to examine the functional diversity of piriform cortex interneurons (PC; an area of the brain that easily supports seizures) before and after kindling-induced epilepsy. Using cluster analysis, we found five control firing behaviors. These groups were termed: non-adapting very high frequency (NAvHF), adapting high frequency (AHF), adapting low frequency (ALF), strongly adapting low frequency (sALF), and weakly adapting low frequency (wALF). A morphological analysis showed these spiking patterns were not associated with any specific interneuronal morphology although we found that most of the cells displaying NAvHF firing pattern were multipolar. After kindling about 40% of interneuronal firing pattern changed, and neither the NAvHF nor the wALF phenotypes were found. We also found that in multipolar interneurons a long-lasting potassium current was increased. A qPCR analysis indicated Kv1.6 subtype was up-regulated after kindling. An immunocytochemical analysis showed that Kv1.6 protein expression on parvalbumin (multipolar) interneurons increased by greater than 400%. We also examined whether these changes could be due to the selective death of a subset of interneurons but found that there was no change in cell number. These data show an important loss of the functional diversity of interneurons in the PC. Our data suggest that under pathophysiological condition interneurons are plastic resulting in the attenuation of high frequency network oscillations in favor of low frequency network activity. This may be an important new mechanism by which network synchrony is disturbed in epileptic seizures.
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PMID:The loss of interneuron functional diversity in the piriform cortex after induction of experimental epilepsy. 2280 Oct 84