The Anx7(+/-) knockout mutation alters electrical and secretory responses to Ca 2+ -mobilizing agents in pancreatic β-cells

David Mears*, Charles L. Zimliki, Illani Atwater, Eduardo Rojas, Mirta Glassman, Ximena Leighton, Harvey B. Pollard, Meera Srivastava

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Insulin secretion from the pancreatic β-cell is controlled by changes in membrane potential and intracellular Ca 2+ . The contribution of intracellular Ca 2+ stores to this process is poorly understood. We have previously shown that β-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express reduced levels of IP 3 receptors and defects in IP 3 -dependent Ca 2+ signaling. To further elucidate the effect of the Anx7(+/-) mutation on signaling related to intracellular Ca 2+ stores in the β-cell, we measured the effects of Ca 2+ mobilizing agents on electrical activity, intracellular Ca 2+ and insulin secretion in control and mutant β-cells. We found that the muscarinic agonist carbachol and the ryanodine receptor agonists caffeine and 4-chloro-m-cresol had more potent depolarizing effects on Anx7(+/-) β-cells compared to controls. Accordingly, glucose-induced insulin secretion was augmented to a greater extent by caffeine in mutant islets. Surprisingly, ryanodine receptor-mediated Ca 2+ mobilization was not affected by the Anx7(+/-) mutation, suggesting that the mechanism underlying the observed differences in electrical and secretory responsiveness does not involve intracellular Ca 2+ stores. Our results provide evidence that both IP 3 receptors and ryanodine receptors play important roles in regulating β-cell membrane potential and insulin secretion, and that the Anx7(+/-) mutation is associated with alterations in the signaling pathways related to these receptors.

Original languageEnglish
Pages (from-to)697-704
Number of pages8
JournalCellular Physiology and Biochemistry
Issue number5-6
StatePublished - Jun 2012
Externally publishedYes


  • Annexin 7
  • Endoplasmic reticulum
  • Insulin secretion
  • Islet of langerhans
  • Knockout mouse
  • Ryanodine receptor
  • Stimulus-secretion coupling


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