The blockade of K(+)-ATP channels has neuroprotective effects in an in vitro model of brain ischemia.
There is a common belief that the opening of K(+)-ATP channels during an ischemic episode has protective effects on neuronal functions by inducing a reduction in energy consumption. However, recent studies have also proposed that activation of these channels might have deleterious effects on cell's survival possibly after a stroke or during long-lasting neurodegenerative processes. Considering these contrasting results, we have used a hippocampal in vitro slice preparation in order to investigate the possible effects of K(+)-ATP channel blockers on the electrophysiological and morphological changes induced by a transient episode of ischemia (oxygen and glucose deprivation) on CA1 pyramidal neurons. Therefore, we found that tolbutamide and glibenclamide, both nonselective K(+)-ATP channel blockers, produce neuroprotective effects against in vitro ischemia. Interestingly, the mitochondrial K(+)-ATP channel blocker 5-hydroxydecanoate and various K(+) channel blockers did not exert neuroprotection. Our results are consistent with the concept that a decreased activity of the plasmalemmal K(+)-ATP conductances may have a protective effect during episodes of transient cerebral ischemia.
Department of Experimental Neurology, S. Lucia Foundation IRCCS, Rome, Italy.
Robert
R
Nisticò
Silvia
S
Piccirilli
L
L
Sebastianelli
Giuseppe
G
Nisticò
G
G
Bernardi
N B
NB
Mercuri
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000473:pathology; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D054086:KATP Channels; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D005947:Glucose