Study of a glycine hinge in ATP-sensitive potassium channels

Potassium channels regulate cell excitability by gating K⁺ flux through transmembrane pores. Inward rectifier (Kir) channels, including ATP-sensitive K⁺ (KATP) channels, rely on TM2 flexibility for gating, hypothesized to involve a glycine hinge. This study examined glycine mutations linked to congenital hyperinsulinism. Glycine-to-arginine substitution abolished conduction via electrostatic disruption, while a compensatory mutation restored function without affecting nucleotide regulation, indicating the hinge is not essential for gating. Glycine-to-proline mutation caused inactivation, likely due to impaired coupling between cytoplasmic and transmembrane domains. Findings refine the hinge hypothesis and advance understanding of Kir channel gating and disease mechanisms.