Electrophysiology of Endolysosomal Two-Pore Channels: A Current Account.

ABSTRACT: Two-pore channels TPC1 and TPC2 are ubiquitously expressed pathophysiologically relevant proteins that reside on endolysosomal vesicles. Here, we review the electrophysiology of these channels. Direct macroscopic recordings of recombinant TPCs expressed in enlarged lysosomes in mammalian cells or vacuoles in plants and yeast demonstrate gating by the Ca²⁺-mobilizing messenger NAADP and/or the lipid PI(3,5)P₂. TPC currents are regulated by H⁺, Ca²⁺, and Mg²⁺ (luminal and/or cytosolic), as well as protein kinases, and they are impacted by single-nucleotide polymorphisms linked to pigmentation. Bisbenzylisoquinoline alkaloids, flavonoids, and several approved drugs demonstrably block channel activity. Endogenous TPC currents have been rec

SUBMITTER: Patel S 

PROVIDER: S-EPMC9368155 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature