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Titolo:
Effects of ion channel blockade on the distribution of Na, K, Ca and otherelements in oxygen-glucose deprived CA1 hippocampal neurons
Autore:
Lopachin, RM; Gaughan, CL; Lehning, EJ; Weber, ML; Taylor, CP;
Indirizzi:
Montefiore Med Ctr, Albert Einstein Coll Med, Dept Anesthesiol, Bronx, NY 10467 USA Montefiore Med Ctr Bronx NY USA 10467 pt Anesthesiol, Bronx, NY 10467 USA Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Dept Neurosci Therapeut, Ann Arbor, MI 48105 USA Warner Lambert Parke Davis Ann Arbor MI USA48105 Ann Arbor, MI 48105 USA
Titolo Testata:
NEUROSCIENCE
fascicolo: 4, volume: 103, anno: 2001,
pagine: 971 - 983
SICI:
0306-4522(2001)103:4<971:EOICBO>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
X-RAY-MICROANALYSIS; SCANNING ELECTRON-MICROSCOPY; FROZEN-HYDRATED SECTIONS; FOCAL CEREBRAL-ISCHEMIA; IN-VITRO ISCHEMIA; OXYGEN/GLUCOSE DEPRIVATION; BRAIN TEMPERATURE; CALCIUM CHANNELS; ANOXIC DAMAGE; OPTIC-NERVE;
Keywords:
ischemia; reperfusion; neurodegeneration; neuroprotection; voltage-gated ion channels; ionotropic glutamate receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Lopachin, RM Montefiore Med Ctr, Albert Einstein Coll Med, Dept Anesthesiol, Bronx, NY 10467 USA Montefiore Med Ctr Bronx NY USA 10467 l, Bronx, NY 10467 USA
Citazione:
R.M. Lopachin et al., "Effects of ion channel blockade on the distribution of Na, K, Ca and otherelements in oxygen-glucose deprived CA1 hippocampal neurons", NEUROSCIENC, 103(4), 2001, pp. 971-983

Abstract

The pathophysiology of brain ischemia and reperfusion injury involves perturbation of intraneuronal ion homeostasis. To identify relevant routes of ion flux, rat hippocampal slices were perfused with selective voltage- or ligand-gated ion channel blockers during experimental oxygen-glucose deprivation and subsequent reperfusion. Electron probe X-ray microanalysis was usedto quantitate water content and concentrations of Na, K, Ca and other elements in morphological compartments (cytoplasm, mitochondria and nuclei) of individual CAI pyramidal cell bodies. Blockade of voltage-gated channel-mediated Na+ entry with tetrodotoxin (1 muM) or lidocaine (200 muM) significantly reduced excess intraneuronal Na and Ca accumulation in all compartmentsand decreased respective K loss. Voltage-gated Ca2+ channel blockade with the L-type antagonist nitrendipine (10 muM) decreased Ca entry and modestlypreserved CA1 cell elemental composition and water content. However, a lower concentration of nitrendipine (1 IJ M) and the N-, P-subtype Ca2+ channel blocker omega -conotoxin MVIIC (3 muM) were ineffective. Glutamate receptor blockade with the N-methyl-D-aspartate (NMDA) receptor-subtype antagonist 3-(2-carboxypiperazin-4-yl) propyl-l-phosphonic acid (CPP; 100 muM) or the alpha-amino-3-hydroxy-5-methyl-4-isoazole propionic acid (AMPA) receptor subtype blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 muM/ 100 muMglycine) completely prevented Na and Ca accumulation and partially preserved intraneuronal K concentrations. Finally, the increase in neuronal water content normally associated with oxygen-glucose deprivation/reperfusion wasprevented by Na+ channel or glutamate receptor blockade. Results of the present study demonstrate that antagonism of either postsynaptic NMDA or AMPA glutaminergic receptor subtypes provided nearly completeprotection against ion and water deregulation in nerve cells subjected to experimental ischemia followed by reperfusion. This suggests activation of ionophoric glutaminergic receptors is involved in loss of neuronal osmoregulation and ion homeostasis. Na+ channel blockade also effectively diminished neuronal ion and water derangement during oxygen-glucose deprivation and reperfusion. Prevention of elevated Na: levels is likely to provide neuroprotection by decreasing presynaptic glutamate release and by improving cellular osmoregulation, adenosine triphosphate utilization and Ca2+ clearance. Thus, we suggest that voltage-gated tetrodotoxin-sensitive Na+ channels andglutamate-gated ionotropic NMDA or AMPA receptors are important routes of ion flux during nerve cell injury induced by oxygen-glucose deprivation/reperfusion. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

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Documento generato il 30/03/20 alle ore 08:32:05