The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons.

ABSTRACT: Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH₅₀ of 5.5. whereas internal protons inhibit TRPM3 with an inhibitory pH₅₀ of 6.9. We identified three titratable residues, D1059, D1062, and D1073, at the vestibule of the channel pore that contributes to pH sensitivity. The mutation of D1073Q reduced TRPM3 current by lo

SUBMITTER: Hossain Saad MZ 

PROVIDER: S-EPMC7884864 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature