Coincidence of early glucose‐induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic beta‐cells.

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Abstract
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.

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