Stromal Interaction Molecule 1 (STIM1) Regulates ATP-sensitive Potassium (KATP) and Store-operated Ca2+ Channels in MIN6 β-Cells

Abstract

Stromal interaction molecule 1 (STIM1) regulates store-operated Ca²⁺ entry (SOCE) and other ion channels either as an endoplasmic reticulum Ca²⁺-sensing protein or when present in the plasma membrane. However, the role of STIM1 in insulin-secreting β-cells is unresolved. We report that lowering expression of <i>STIM1</i>, the gene that encodes STIM1, in insulin-secreting MIN6 β-cells with RNA interference inhibits SOCE and ATP-sensitive K⁺ (<i>K</i>_ATP) channel activation. The effects of <i>STIM1</i> knockdown were reversed by transduction of MIN6 cells with an adenovirus gene shuttle vector that expressed human <i>STIM1</i> Immunoprecipitation studies revealed that STIM1 binds to nucleotide binding fold-1 (NBF1) of the sulfonylurea receptor 1 (SUR1) subunit of the <i>K</i>_ATP channel. Binding of STIM1 to SUR1 was enhanced by poly-lysine. Our data indicate that SOCE and <i>K</i>_ATP channel activity are regulated by STIM1. This suggests that STIM1 is a multifunctional signaling effector that participates in the control of membrane excitability and Ca²⁺ signaling events in β-cells.