Opening of KATP 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 72 h, 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. NeuroReport 11:463-465. (C) 2000 Lippincott Williams & Wilkins.