Activation of ATP-sensitive potassium channels decreases neuronal injury caused by chemical hypoxia.
Cerebral ischemia is known to induce endogenous adaptive mechanisms such as the activation of ATP-sensitive potassium channels that can prevent or delay neuronal injury. This process can be therapeutically mimicked by treatment with potassium channel openers. Primary neuronal cell cultures were derived from embryonic chick telencephalon and were exposed to chemical hypoxia (1 mM cyanide) or excitotoxic injury (1 mM L-glutamate). While treatments with the potassium channel openers bimakalim (1-10 microM) and EMD 57283 (0.1-10 microM) were clearly able to maintain neuronal viability after chemical hypoxia, similar concentrations of the drugs had negligible effects on glutamate-induced neurotoxicity. In contrast, both types of neuronal injury were sensitive to the protective action of the glutamate receptor antagonist dizocilpine (MK-801; 0.1-1 microM). The neuroprotective effect of bimakalim against chemically induced hypoxic injury was reversed by tolbutamide (1 microM), an ATP-sensitive potassium channel blocker. These experiments demonstrate neuroprotective effects of potassium channel openers that could be related to inhibition of neurotransmitter release.
Wind
T
T
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Philipps-University, Marburg/Lahn, Germany.
Prehn
J H
JH
Peruche
B
B
Krieglstein
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D004095:Dihydropyridines / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D012966:Sodium Cyanide
D001578:Benzopyrans; D004095:Dihydropyridines; C107488:EMD 57283; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D015221:Potassium Channels; D011724:Pyridazines; D018698:Glutamic Acid; C061050:bimakalim; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D012966:Sodium Cyanide