Activation of ATP-sensitive potassium channels as an element of the neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen glucose deprivation.
NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been reported in preclinical models of ischemia to induce neuroprotection and neuroplasticity. This work shows the effects of MLC901 on an in vitro model of oxygen glucose deprivation (OGD). MLC901 prevents neuronal death induced by 120 min OGD and decreases the exaggerated Ca²⁺ entry in mature cortical neurons exposed to 120 min OGD. The neuroprotective effect of MLC901 is associated with a large hyperpolarization of ∼20 mV which is antagonized by glibenclamide, the specific inhibitor of K(ATP) channels. In addition MLC901 strengthens the activation of K(ATP) channels. MLC901 has been directly shown to act as an activator of K(ATP) channels as potent as the classical K(ATP) channel opener. The capacity of MLC901 to produce a large hyperpolarization, particularly in neurons that have suffered from energy deprivation probably plays an important role in the neuroprotective effects of this traditional medicine that comes in addition to its previously demonstrated neuroregenerative properties.
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS, UMR6097), Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
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Moha Ou Maati
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Borsotto
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Chatelain
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Widmann
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Lazdunski
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Heurteaux
D000818:Animals; D019556:COS Cells; D020013:Calcium Signaling / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005947:Glucose / Q000378:metabolism*; D054086:KATP Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats
D004365:Drugs, Chinese Herbal; D054086:KATP Channels; D049990:Membrane Transport Modulators; D009419:Nerve Tissue Proteins; C546417:Neuroaid; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D005947:Glucose