Neuroprotective effects of omega-Aga-IVA against in vitro ischaemia in the rat hippocampal slice.
Excessive accumulation of Ca2+ in neurones and glutamate release are involved in neuropathological processes, including ischaemia. We investigated the neuroprotective effects of the Ca2+ channel antagonist, omega-Aga-IVA, in CA1 pyramidal neurones in rat hippocampal slices following an in vitro hypoxic-hypoglycaemic insult. Following this insult, evoked post-synaptic response amplitudes decreased from 3.7 +/- 0.5 mV to 0.6 +/- 0.2 mV and the CA1 neurones appeared dead using a live/dead fluorescence assay with confocal microscopy. Slices treated with 200 nM omega-Aga-IVA had evoked response amplitudes not significantly different from control (3.3 +/- 0.5 mV) and the CA1 neurones appeared viable using the live/dead fluorescence assay. The neuroprotective efficacy of omega-Aga-IVA suggests that omega-Aga-IVA-sensitive Ca2+ channels participate in ischaemic neuronal death and constitute a potential target of therapeutic intervention.
University of Ottawa, Ontario, Canada.
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Small
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Monette
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Mealing
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Buchan
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Morley
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology*; D020867:omega-Agatoxin IVA
D002121:Calcium Channel Blockers; D013111:Spider Venoms; D020867:omega-Agatoxin IVA