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Titolo:
Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K alpha and pandinustoxin-K alpha
Autore:
Juhng, KN; Kokate, TG; Yamaguchi, S; Kim, BY; Rogowski, RS; Blaustein, MP; Rogawski, MA;
Indirizzi:
NINCDS,92euronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 208 NINCDS Bethesda MD USA 20892 , Epilepsy Res Branch, NIH, Bethesda, MD 208 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 ept Physiol, Baltimore, MD 21201 USA
Titolo Testata:
EPILEPSY RESEARCH
fascicolo: 2-3, volume: 34, anno: 1999,
pagine: 177 - 186
SICI:
0920-1211(199904)34:2-3<177:IOSBTP>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED POTASSIUM CHANNELS; HIPPOCAMPUS IN-VITRO; EPILEPTIFORM ACTIVITY; RAT HIPPOCAMPUS; ANTICONVULSANT DRUGS; GYKI 52466; 4-AMINOPYRIDINE; DENDROTOXIN; NEURONS; SYNAPTOSOMES;
Keywords:
pandinustoxin-K alpha; tityustoxin-K alpha; 4-aminopyridine; paxilline; K+ channel blocker; AMPA receptor antagonist;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Rogawski, MA NINCDS,250,10nal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N- NINCDS Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408 Bethesda MD USA 20892
Citazione:
K.N. Juhng et al., "Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K alpha and pandinustoxin-K alpha", EPILEPSY R, 34(2-3), 1999, pp. 177-186

Abstract

The scorpion venom peptide toxins tityustoxin-K alpha (TsTx-K alpha) and pandinustoxin-K alpha (PiTx-K alpha) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K alpha preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K alpha is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K+ channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists il-aminopyridine (4-AP),an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca2+-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K alpha and PiTx-K alpha in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K alpha and PiTx-K alpha were 9 and 33 ng, respectively. 4-AP produced seizure activity similar tothe toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 mu g. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca2+-activatedK+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 03:15:38