Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single episode of status epilepticus (SE) causes numerous structural and functional changes in the brain that can lead to the development of a chronic epileptic condition. Most studies of this plasticity have focused on changes in excitatory and inhibitory synaptic properties. However, the intrinsic firing properties that shape the output of the neuron to a given synaptic input may also be persistently affected by SE. Thus, 54% of CA1 pyramidal cells, which normally fire in a regular mode, are persistently converted to a bursting mode after an episode of SE induced by the convulsant pilocarpine. In this model, intrinsic bursts evoked by threshold-straddling depolarizations, and their underlying spike afterdepolarizations (ADPs), were resistant to antagonists of N-, P/Q-, or L-type Ca2+ channels but were readily suppressed by low (30-100 microm) concentrations of Ni2+ known to block T- and R-type Ca2+ channels. The density of T-type Ca2+ currents, but not of other pharmacologically isolated Ca2+ current types, was upregulated in CA1 pyramidal neurons after SE. The augmented T-type currents were sensitive to Ni2+ in the same concentration range that blocked the novel intrinsic bursting in these neurons (IC50 = 27 microm). These data suggest that SE may persistently convert regular firing cells to intrinsic bursters by selectively increasing the density of a Ni2+-sensitive T-type Ca2+ current. This nonsynaptic plasticity considerably amplifies the output of CA1 pyramidal neurons to synaptic inputs and most probably contributes to the development and expression of an epileptic condition after SE.
 ...
PMID:Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus. 1197 40

Toxic causes of seizures are numerous: alcohol and other substances of abuse, drugs, and industrial and household products. However, in the absence of a clearly suggestive history and/or associated symptoms and signs, identification of the toxic origin of new-onset seizures may be extremely difficult. We report here the case of a patient admitted in our hospital after a single generalized tonic-clonic seizure. The remarkable coincidence that a colleague of his, with whom he was working to clean the same workshop, had been admitted 1 week earlier for respiratory distress, coma, and de novo nonconvulsive focal status epilepticus, led us to consider a possible toxicologic etiology. Urine analysis revealed a high nickel concentration, suggestive of acute nickel poisoning.
 ...
PMID:First epileptic seizure induced by occupational nickel poisoning. 1594 40

Extracellular zinc can induce numerous acute and persistent physiological and toxic effects in neurons by acting at their plasma membrane or intracellularly following permeation or uptake into them. Zinc acutely and reversibly blocks T-type voltage-gated calcium current (I(CaT)), but the long-term effect of zinc on this current has not been studied. Because chemically induced status epilepticus (SE) results in the release of zinc into the extracellular space, as well as in a long-lasting increase in I(CaT) in CA1 pyramidal cells, we hypothesized that zinc may play a causative role in I(CaT) upregulation. We tested this hypothesis by monitoring for 18 days the effects of zinc and ibotenic acid (a neurotoxic agent serving as control for zinc), injected into the right lateral ventricle, on I(CaT) in rat CA1 pyramidal cells. Both zinc and ibotenic acid caused marked hippocampal lesions on the side of injection, but only minor damage to contralateral hippocampi. Zinc, but not ibotenic acid, caused upregulation of a nickel-sensitive I(CaT) in a subset of contralateral CA1 pyramidal cells, appearing 2 days after injection and lasting for about 2 weeks thereafter. In contrast, acute application of zinc to CA1 pyramidal cells promptly blocked I(CaT). These data indicate that extracellular zinc has a dual effect on I(CaT), blocking it acutely while causing its long-term upregulation. Through the latter effect, zinc may regulate the intrinsic excitability of principal neurons, particularly in pathological conditions associated with enhanced release of zinc, such as SE.
 ...
PMID:Zinc induces long-term upregulation of T-type calcium current in hippocampal neurons in vivo. 2293 Feb 74