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Influence of Cholesterol on Cellular Signaling and Fusion Pore Kinetics

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Abstract

Cholesterol is an important lipid component of cellular membranes. Recent studies have shown that changes in cellular cholesterol level can affect cellular functions. Here, we summarize our recent findings on the impact of cholesterol on the glucose-stimulated Ca2+ signaling in rat pancreatic β cells and the fusion pore kinetics of large dense core granules in rat chromaffin cells. In mouse pancreatic β cells, pharmacological elevation of cellular cholesterol (but not cholesterol extraction) reduced the current density of the delayed rectifier K+ channels, the ATP-dependent K+ channels, and voltage-gated Ca2+ channels. Importantly, cholesterol enrichment impaired glucose-stimulated Ca2+ signaling in mouse pancreatic β cells via a suppression of voltage-gated Ca2+ channels and a decrease in mitochondrial ATP production, which in turn led to a reduction in the glucose-evoked depolarization. In rat chromaffin cells, we found that the persistence of the semi-stable fusion pore was increased by cholesterol enrichment, and acute cholesterol extraction from the cytosolic side of the cell destabilized the semi-stable fusion pore. Overall, our findings highlight the importance of cholesterol in the regulation of cellular signaling and exocytosis.

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Acknowledgments

This work was supported by research grants from the Canadian Institute of Health Research (to A. Tse) and the National Science and Engineering Research Council (to F. Tse).

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Authors and Affiliations

  1. Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2H7

    Amy Tse, Andy K. Lee & Frederick W. Tse

  2. Centre for Neuroscience, University of Alberta, Edmonton, Canada, T6G 2H7

    Amy Tse, Lei Yan & Frederick W. Tse

  3. Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G 2H7

    Amy Tse

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  1. Amy Tse
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  2. Andy K. Lee
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  4. Frederick W. Tse
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Correspondence to Frederick W. Tse.

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Tse, A., Lee, A.K., Yan, L. et al. Influence of Cholesterol on Cellular Signaling and Fusion Pore Kinetics. J Mol Neurosci 48, 395–401 (2012). https://doi.org/10.1007/s12031-012-9760-2

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  • DOI: https://doi.org/10.1007/s12031-012-9760-2

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