Opening of K(ATP) channels is mandatory for acquisition of ischemic tolerance by adenosine.
Binding of adenosine to neuronal adenosine receptors activates a signal transduction pathway (the adenosine mechanism), leading to a temporary ischemic tolerance. We have demonstrated before that induction of this mechanism in primary rat neuronal cultures, by activation of adenosine receptors, or by activation of protein kinase C (PKC), confers a wide time window of ischemic tolerance, lasting up to 72h, the early (immediate) part of which depends on opening of K(ATP) channels (glibenclamide sensitive). Here we demonstrate that the entire duration of the ischemic tolerance conferred by activation of the adenosine mechanism depends on opening of the K(ATP) channels. Thus, opening of the K(ATP) channels appears to be a mandatory step in the adenosine mechanism, leading to the creation of the wide time window of ischemic tolerance.
Reshef
A
A
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Sperling
O
O
Zoref-Shani
E
E
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D016923:Cell Death; D002478:Cells, Cultured; D005905:Glyburide / Q000494:pharmacology; D019194:Ischemic Preconditioning; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats / Q000196:embryology; D012016:Reference Values; D015427:Reperfusion Injury / Q000473:pathology
D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D000241:Adenosine; D005905:Glyburide