Opening of KATP channels is mandatory for acquisition of ischemic tolerance by adenosine

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Abstract
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.