β cell store-operated ion channels

Abstract

Signaling molecules produced in the pancreatic β-cell following mitochondrial oxidation of glycolytic intermediate metabolites and oxidative phosphorylation trigger Ca 2+ -dependent signaling pathways that regulate insulin exocytosis. Much is known about ATP-sensitive K + and voltage-gated Ca 2+ currents that contribute to Ca 2+ -dependent signal transduction in β-cells and insulin secretion, but relatively little is known about other Ca 2+ channels that regulate β-cell Ca 2+ signaling dynamics and insulin secretion. In a wide range of eukaryotic cells, store-operated Ca 2+ entry (SOCE) plays a critical role regulating spatial and temporal changes in cytoplasmic Ca 2+ concentration, endoplasmic reticulum (ER) Ca 2+ homeostasis, gene expression, protein biosynthesis, and cell viability. Although SOCE has been proposed to play important roles in β-cell Ca 2+ signaling and insulin secretion, the underlying molecular mechanisms remain undefined. In this chapter, we provide both an overview of our current understanding of ionic currents regulated by ER Ca 2+ stores in insulin-secreting cells and a review of studies in other cell systems that have identified the molecular basis and regulation of SOCE.