ORIGIN OF SLOW AND FAST OSCILLATIONS OF CA2-ISLETS( IN MOUSE PANCREATIC)

1. Pancreatic islets exposed to 11 mM glucose exhibited complex variat ions of cytoplasmic Ca2+ concentration ([Ca2+](i)) with slow (0.3-0.9 min(-1)) or fast (2-7 min(-1)) oscillations or with a mixed pattern. 2 . Using digital imaging and confocal microscopy we demonstrated that t he mixed pattern with slow and superimposed fast oscillations was due to separate cell populations with the respective responses. 3. In isle ts with mixed [Ca2+](i) oscillations, exposure to the sarcoplasmic-end oplasmic reticulum Ca2+-ATPase inhibitors thapsigargin or 2,5-di-tert- butylhydroquinone (DTBHQ) resulted in a selective disappearance of the fast pattern and amplification of the slow pattern. 4. In addition, t he protein kinase A inhibitor R-p-cyclic adenosine 3',5'-monophosphoro thioate sodium salt transformed the mixed [Ca2+](i) oscillations into slow oscillations with larger amplitude. 5. Islets exhibiting only slo w oscillations reacted to law concentrations of glucagon with inductio n of the fast or the mixed pattern. In this case the fast oscillations were also counteracted by DTBHQ. 6. The spontaneously occurring fast oscillations seemed to require the presence of cAMP-elevating glucagon , since they were more common in large islets and suppressed during cu lture. 7. Image analysis revealed [Ca2+](i) spikes occurring irregular ly in time and space within an islet. These spikes were preferentially observed together with fast [Ca2+](i) oscillations, and they became m ore common after exposure to glucagon. 8. Both the slow and fast oscil lations of [Ca2+](i) in pancreatic islets rely on periodic entry of Ca 2+. However, the fast oscillations also depend in some way on paracrin e factors promoting mobilization of Ca2+ from intracellular stores. It is proposed that such a mobilization in different cells within a tigh tly coupled islet syncytium generates spikes which co-ordinate the reg ular bursts of action potentials underlying the fast oscillations.