Targeting of Voltage-Gated K+ and Ca2+ Channels and Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor Proteins to Cholesterol-Rich Lipid Rafts in Pancreatic α-Cells: Effects on Glucagon Stimulus-Secretion Coupling

Pancreatic α-cells secrete glucagon in response to low glucose to counter insulin actions, thereby maintaining glucose homeostasis. The molecular basis of α-cell stimulus-secretion coupling has not been fully elucidated. We investigated the expression of voltage-gated K+ (KV) and Ca2+ (CaV) channels, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in pancreatic α-cells and examined their targeting to specialized cholesterol-rich lipid rafts. In α-cells, we detected the expression of KV4.1/4.3 (A-type current), KV3.2/3.3 (delayed rectifier current), CaV1.2 (L-type current), CaV2.2 (N-type current), and the SNARE (synaptosomal-associated protein of 25 kDa, syntaxin 1A, and vesicle-associated membrane protein 2) and SNARE-associated proteins (Munc-13–1 and Munc-18a). We also detected caveolin-2, a structural protein of cholesterol-rich lipid rafts. Of these proteins, caveolin-2, KV4.1/4.3, CaV1.2, and SNARE proteins (syntaxin 1A, synaptosomal-associated protein of 2...