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. 1992 Sep;455:173–186. doi: 10.1113/jphysiol.1992.sp019295

The relationship between glucose-induced K+ATP channel closure and the rise in [Ca2+]i in single mouse pancreatic beta-cells.

M Valdeolmillos 1, A Nadal 1, D Contreras 1, B Soria 1
PMCID: PMC1175638  PMID: 1484353

Abstract

1. Intracellular calcium [Ca2+]i and channel activity were simultaneously recorded in single, dissociated mouse beta-cells kept in culture for 1-3 days. [Ca2+]i was estimated from microfluorometric ratio methods using Indo-1. Channel activity was measured using the cell-attached configuration of the patch-clamp technique. 2. At low glucose concentrations (0.3 mM), resting K+ATP channel activity was prevalent. Increasing glucose up to 16 mM, produced a gradual decrease in K+ATP channel activity over a time course of 90-120 s (temperature = 23 degrees C) and an increase in [Ca2+]i. 3. In the majority of experiments, glucose elicited biphasic action currents (action potentials) which preceded the rise in [Ca2+]i. There was a close correlation between spike frequency and the levels of [Ca2+]i. 4. The sulphonylurea tolbutamide (1 mM) blocked K+ATP channels in 10-20 s. K+ATP channel blockade was associated with a quick rise in [Ca2+]i. 5. When K+ATP channel activity was stimulated in the presence of diazoxide (100 microM), increasing the glucose concentration from 3 to 16 mM produced a decrease in [Ca2+]i. Only when diazoxide was removed did glucose produce an increase in [Ca2+]i. 6. In a small population of cells, glucose (16 mM) produced a small decrease in K+ATP channel activity but not an increase in [Ca2+]i. In such cells, tolbutamide blocked K+ATP channels and produced an increase in [Ca2+]i. 7. These results demonstrate a close correlation between K+ATP channel activity and [Ca2+]i in beta-cells. The findings are consistent with the model in which glucose metabolism produces a rise in [Ca2+]i through the blockade of K+ATP channels, membrane depolarization and calcium current activation.

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Selected References

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