Transient Morphological Alterations in the Hippocampus After Pentylenetetrazole-Induced Seizures in Rats.

The relationships between seizures, neuronal death, and epilepsy remain one of the most disputed questions in translational neuroscience. Although it is broadly accepted that prolonged and repeated seizures cause neuronal death and epileptogenesis, whether brief seizures can produce a mild but similar effect is controversial. In the present work, using a rat pentylenetetrazole (PTZ) model of seizures, we evaluated how a single episode of clonic-tonic seizures affected the viability of neurons in the hippocampus, the area of the brain most vulnerable to seizures, and morphological changes in the hippocampus up to 1 week after PTZ treatment (recovery period).

Complex action of tyramine, tryptamine and histamine on native and recombinant ASICs.

Proton-gated channels of the ASIC family are widely distributed in the mammalian brain, and, according to the recent data, participate in synaptic transmission. However, ASIC-mediated currents are small, and special efforts are required to detect them. This prompts the search for endogenous ASIC ligands, which can activate or potentiate these channels.

Histamine selectively potentiates acid-sensing ion channel 1a.

Although acid-sensitive ion channels (ASICs) play an important role in brain functions, the exact mechanism of their physiological activation remain unclear. A possible answer to the intriguing question is that some presently unknown endogenous ligand(s) positively modulate ASICs and enhance their responses to physiologically significant level. In the present work we found that histamine selectively potentiates ASIC1a homomers in CHO cells.

Status epilepticus alters hippocampal long-term synaptic potentiation in a rat lithium-pilocarpine model.

Seizure-induced memory deficits are frequent in patients with temporal lobe epilepsy. However, the neural mechanisms responsible for this memory impairment are not entirely clear. Persistent changes in synaptic efficacy, long-term potentiation (LTP), and depression are considered a cellular substrate underlying the learning and memory processes.

Determinants of action of hydrophobic amines on ASIC1a and ASIC2a.

Acid-sensing ion channels (ASICs) are involved in numerous physiological and pathological processes in the central nervous system. Development of pharmacological tools capable to inhibit or potentiate these channels is important for our knowledge about roles of ASICs in the neuronal network and can be promising for treatment of some disorders. Recently we described four hydrophobic monoamines that potentiate and inhibit ASICs depending on subunit composition of the channel and peculiarities of the drug structure.

Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study.

N-methyl-D-aspartate receptor channel blockers prevent pentylenetetrazole-induced convulsions and morphological changes in rat brain neurons.

Alterations in inhibitory and excitatory neurotransmission play a central role in the etiology of epilepsy, with overstimulation of glutamate receptors influencing epileptic activity and corresponding neuronal damage. N-methyl-D-aspartate (NMDA) receptors, which belong to a class of ionotropic glutamate receptors, play a primary role in this process. This study compared the anticonvulsant properties of two NMDA receptor channel blockers, memantine and 1-phenylcyclohexylamine (IEM-1921), in a pentylenetetrazole (PTZ) model of seizures in rats and investigated their potencies in preventing PTZ-induced morphological changes in the brain.

A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities.

CsTx-1, the main neurotoxic acting peptide in the venom of the spider Cupiennius salei, is composed of 74 amino acid residues, exhibits an inhibitory cysteine knot motif, and is further characterized by its highly cationic charged C terminus. Venom gland cDNA library analysis predicted a prepropeptide structure for CsTx-1 precursor. In the presence of trifluoroethanol, CsTx-1 and the long C-terminal part alone (CT1-long; Gly-45-Lys-74) exhibit an α-helical structure, as determined by CD measurements.

Influence of external magnesium ions on the NMDA receptor channel block by different types of organic cations.

The NMDA type of ionotropic glutamate receptors plays a unique role in synaptic functions because of high permeability for calcium and because of a voltage-dependent block by endogenous Mg(2+). Activity and voltage dependence of the NMDA receptor channel block by organic cations are strongly affected by competition with magnesium ions for the binding site in the channel pore. It complicates prediction of action of NMDA receptor channel blockers in vivo.

Novel class of spider toxin: active principle from the yellow sac spider Cheiracanthium punctorium venom is a unique two-domain polypeptide.

Venom of the yellow sac spider Cheiracanthium punctorium (Miturgidae) was found unique in terms of molecular composition. Its principal toxic component CpTx 1 (15.1 kDa) was purified, and its full amino acid sequence (134 residues) was established by protein chemistry and mass spectrometry techniques.

Common binding site for externally and internally applied AMPA receptor channel blockers.

Adamantane derivative IEM-1676 (Ad-N(+)H(2)-(CH(2))(5)-N(+)Me(3)) causes open-channel block of Ca(2+)-permeable AMPA receptors when applied externally, but internal application results in both closed- and open-channel block. The relationships between blocking action of externally and internally applied IEM-1676 were studied using patch clamp technique. Extracellular action of IEM-1676 was decreased by its intracellular application, thus suggesting that the binding sites of the externally and internally applied drug coincide or at least overlap significantly.

Blockade of NMDA receptor channels by 9-aminoacridine and its derivatives.

9-Aminoacridine is known as "foot-in-the-door" NMDA receptor channel blocker because its binding prevents channel closure. Structural determinants of this mechanism of block were studied using a series of 9-aminoacridine derivatives. Experiments were performed on native NMDA receptors of hippocampal pyramidal neurons, isolated from rat brain slices.

Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneurons.

The inhibitory action of non-steroid anti-inflammatory drugs was investigated on acid-sensing ionic channels (ASIC) in isolated hippocampal interneurons and on recombinant ASICs expressed in Chinese hamster ovary (CHO) cells. Diclofenac and ibuprofen inhibited proton-induced currents in hippocampal interneurons (IC(50) were 622 +/- 34 muM and 3.42 +/- 0.

Modulation of the kinetics of evoked quantal release at mouse neuromuscular junctions by calcium and strontium.

The effects of calcium and strontium on the quantal content of nerve-evoked endplate currents and on the kinetic parameters of quantal release (minimal synaptic delay, value of main mode of synaptic delay histogram, and variability of synaptic delay) were studied at the mouse neuromuscular synapse. At low calcium ion concentrations (0.2-0.

Cholinergic regulation of the evoked quantal release at frog neuromuscular junction.

The effects of cholinergic drugs on the quantal contents of the nerve-evoked endplate currents (EPCs) and the parameters of the time course of quantal release (minimal synaptic latency, main modal value of latency histogram and variability of synaptic latencies) were studied at proximal, central and distal regions of the frog neuromuscular synapse. Acetylcholine (ACh, 5 x 10(-4) M), carbachol (CCh, 1 x 10(-5) M) or nicotine (5 x 10(-6) M) increased the numbers of EPCs with long release latencies mainly in the distal region of the endplate (90-120 microm from the last node of Ranvier), where the synchronization of transmitter release was the most pronounced. The parameters of focally recorded motor nerve action potentials were not changed by either ACh or CCh.

Modeling of the pore domain of the GLUR1 channel: homology with K+ channel and binding of channel blockers.

Molecular models of the M2 segments of the GluR1 channel have been elaborated using a molecular mechanics approach. The models are based on the homology between pore-lining segments of AMPA receptor channels and the KcsA K+ channel and on cyclic H bonds at the Q/R site of the AMPA receptor channel. The N-terminal region of an M2 segment of the channel is assumed, like that of the K+ channel, to adopt a helical conformation.