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Coincidence of early glucose-induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic beta-cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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1995 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 485, no 3, 607-617 p.Article in journal (Refereed) Published
Abstract [en]

1. The temporal relationship between the early glucose-induced changes of membrane potential and cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in insulin-releasing pancreatic beta-cells. 2. The mean resting membrane potential and [Ca2+]i were about -70 mV and 60 nM, respectively, in 3 mM glucose. 3. Elevating the glucose concentration to 8-23 mM typically elicited a slow depolarization, which was paralleled by a lowering of [Ca2+]i. When the slow depolarization had reached a threshold of -55 to -40 mV, there was rapid further depolarization to a plateau with superimposed action potentials, and [Ca2+]i increased dramatically. 4. Imposing hyperpolarizations and depolarizations of 10 mV from a holding potential of -70 mV had no detectable effect on [Ca2+]i. Furthermore, glucose elevation elicited a decrease in [Ca2+]i even at a holding potential of -70 mV. 5. Step depolarizations induced [Ca2+]i transients, which decayed with time courses well fitted by double exponentials. The slower component became faster by a factor of about 4 upon elevation of glucose, suggesting involvement of ATP-dependent Ca2+ sequestration or extrusion of [Ca2+]i. 6. Glucose stimulation increased the size and accelerated the recovery of carbachol-triggered [Ca2+]i transients, and thapsigargin, an intracellular Ca(2+)-ATPase inhibitor, counteracted the glucose-induced lowering of [Ca2+]i, indicating that calcium transport into intracellular stores is involved in glucose-induced lowering of [Ca2+]i. 7. The results support the notion that in beta-cells, nutrient-induced elevation of ATP leads initially to ATP-dependent removal of Ca2+ from the cytoplasm, paralleled by a slow depolarization due to inhibition of ATP-sensitive K+ channels. Only after depolarization has reached a threshold do action potentials occur, inducing a sharp elevation in [Ca2+]i.

Place, publisher, year, edition, pages
1995. Vol. 485, no 3, 607-617 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-52912PubMedID: 7562604OAI: oai:DiVA.org:uu-52912DiVA: diva2:80822
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved

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