Opening of K-ATP channels is mandatory for acquisition of ischemic tolerance by adenosine

Binding of adenosine to neuronal adenosine receptors activates a signal tra nsduction pathway (the adenosine mechanism), leading to a temporary ischemi c tolerance. We have demonstrated before that induction of this mechanism i n primary rat neuronal cultures, by activation of adenosine receptors, or b y activation of protein kinase C (PKC), confers a wide time window of ische mic tolerance, lasting up to 72 h, the early (immediate) part of which depe nds on opening of K-ATP channels (glibenclamide sensitive). Here we demonst rate that the entire duration of the ischemic tolerance conferred by activa tion of the adenosine mechanism depends on opening of the K-ATP channels. T hus, opening of the K-ATP channels appears to be a mandatory step in the ad enosine mechanism, leading to the creation of the wide time window of ische mic tolerance. NeuroReport 11:463-465. (C) 2000 Lippincott Williams & Wilki ns.