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Department of Medical Cell Biology, Biomedicum, Uppsala University, SE-751 23 Uppsala, Sweden

(Requests for offprints should be addressed to B Hellman; Email: Bo.Hellman{at}medcellbiol.uu.se)

External ATP is supposed to trigger short-lived increases (transients) of cytoplasmic Ca²⁺ important for entraining insulin-secreting ß-cells into a common rhythm. To get insight into this process, rises of the cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) induced by external ATP were compared with those obtained with acetylcholine, another neurotransmitter with stimulatory effects on the inositol trisphosphate (IP₃) production. A ratiometric fura-2 technique was used for measuring [Ca²⁺]_i in individual ß-cells and small aggregates isolated from ob/ob mouse islets and superfused with a medium containing methoxyverapamil. ATP and acetylcholine induced temporary rises of [Ca²⁺]_I from a basal level manifested as solitary transients (<20 s) and bumps (20 s) superimposed or not with transients. Addition of ATP (1–100 µM) usually triggered transients whereas acetylcholine induced bumps lacking superimposed transients. After the initial rise there was a steady-state elevation of [Ca²⁺]_i in ß-cells exposed to acetylcholine but not to ATP. Similar differences were seen comparing the responses of rat ß-cells to 100 µM ATP and acetylcholine. Inhibition of the sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) pump (with 50 µM cyclopiazonic acid) prevented both the ATP-induced rise of [Ca²⁺]_i and the spontaneous firing of transients. Similar effects were seen after activation of protein kinase C (10 nM phorbol-12-myristate-13-acetate), whereas an inhibitor of this enzyme (2 µM bisindolylmaleimide) promoted the generation of transients. The results indicate that ATP fulfils the demands for a coordinator of the secretory activity of ß-cells by generating distinct [Ca²⁺]_i transients without sustained elevation of basal [Ca²⁺]_i.

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