Glucose-induced electrical activity in rat pancreatic β-cells independent of KATP channel inhibition

University of Sheffield (2001) J Physiol 535P, S054

Communications: Glucose-induced electrical activity in rat pancreatic β-cells independent of KATP channel inhibition

Leonard Best

Department of Medicine, University of Manchester, Oxford Road, Manchester M13 9WL, UK

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KATP channel-independent effects of glucose on electrical activity were studied in pancreatic β-cells isolated from rats (killed by stunning and cervical dislocation) and incubated in the presence of a high concentration of tolbutamide. Electrical activity and input conductance were measured using the ‘perforated patch’ configuration of the patch-clamp technique, and ion channel activity was assessed from perforated patch and cell-attached recordings.

The addition of tolbutamide (500 µM) to cells equilibrated in the absence of glucose resulted in a rapid depolarization and electrical activity followed by a gradual repolarization and disappearence of electrical activity. KATP channel activity, assessed from either whole-cell or cell-attached recordings, remained maximally inhibited throughout exposure to tolbutamide, indicating that repolarization was not due to desensitization of KATP channels to the sulphonylurea. Addition of tetra-ethylammonium chloride (5 mM) in the continued presence of tolbutamide caused a renewed depolarization, suggesting that activation of another K+ conductance probably caused the repolarization.

The application of 16 mM glucose in the continued presence of tolbutamide also caused depolarization of the cells, leading to renewed electrical activity. Input conductance of the cells was reduced by tolbutamide from 1.60 ± 0.02 to 0.46 ± 0.04 nS (P < 0.001), reflecting KATP channel inhibition, but was not further affected by the addition of glucose in the presence of the drug (0.49 ± 0.06 nS). In cells voltage-clamped at -70 mV, addition of glucose in the presence of tolbutamide generated a noisy inward current, probably representing activation of the volume-sensitive anion channel. Consistent with this finding, KATP channel-independent activation of electrical activity by glucose was abolished by the anion channel inhibitor 4, 4Ì-dithiocyanato-stilbene-2, 2Ì-disulphonic acid (100 µM).

It is concluded that glucose can stimulate β-cell electrical activity by a mechanism independent of KATP channel inhibition. This mechanism could involve activation by glucose of the volume-sensitive anion channel.

I should like to thank the NHS executive North-West for financial support.



Where applicable, experiments conform with Society ethical requirements.

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