Variations in ATP-Sensitive K+ Channel Activity Provide Evidence for Inherent Metabolic Oscillations in Pancreatic β-Cells

doi:10.1006/bbrc.1994.2746

Biochemical and Biophysical Research Communications

Volume 205, Issue 1, 30 November 1994, Pages 880-885

https://doi.org/10.1006/bbrc.1994.2746 Get rights and content

Abstract

The cell-attached configuration of the patch clamp technique was used for studying slow variations in the activity of the ATP-sensitive K⁺ channels in pancreatic β-cells isolated from mouse and man. In 0 or 3 mM glucose, the fraction of time the channels were open exhibited oscillations with frequencies in the 0.25-0.40 /min range. This phenomenon is a strong argument for inherent fluctuations in the ATP production of the β-cells. Variations in metabolism may thus be a major determinant for the characteristic large amplitude oscillations of cytoplasmic Ca²⁺ with equivalent frequency.

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Cited by (51)

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Citation Excerpt :
The conclusion drawn from these experiments was that Ca2+ oscillations drive metabolic oscillations, because the latter oscillations stopped when the former were inhibited. However, there is evidence that oscillations in KATP, pO2, or insulin persist in basal glucose (38), or in low Ca2+ (16,17). We report that although Dz can eliminate islet metabolic oscillations, monitored as NAD(P)H fluorescence, in many islets the metabolic oscillations persisted.
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Citation Excerpt :
Two studies performed in low glucose also support the presence of glycolytic oscillations in β-cells. In one study, oscillations were observed in patch-clamp recordings of K(ATP) channel activity (Dryselius et al., 1994). In another, oscillations in the cytosolic Ca2+ concentration were observed in islets at a subthreshold glucose level (Longo et al., 1991).
Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10–60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca²⁺ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic β-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca²⁺ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call “glycolytic bursting.” Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years.

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Regular ArticleVariations in ATP-Sensitive K+ Channel Activity Provide Evidence for Inherent Metabolic Oscillations in Pancreatic β-Cells

Abstract

Regular Article
Variations in ATP-Sensitive K⁺ Channel Activity Provide Evidence for Inherent Metabolic Oscillations in Pancreatic β-Cells