The name tells the story: Two-pore channels

[Display omitted] •Two novel agonists (TPC2-A1-N and TPC2-A1-P) activate two-pore channel 2 (TPC2) with distinct ion selectivities simulating gating of TPC2 by NAADP or PIP2.•The permeability coefficient (PCa/PNa) was about 0.65 for activation of TPC2 with TPC2-A1-N similar to PCa/PNa for NAADP and...

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Bibliographic Details
Published inCell calcium (Edinburgh) Vol. 89; p. 102215
Main Authors Stokłosa, Paulina, Probst, Daniel, Reymond, Jean-Louis, Peinelt, Christine
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.07.2020
Subjects
Agonist
Ion channel selectivity
Lysosomal exocytosis
TMAP
Two-pore channel
Vesicle motility
Ion channel selectivity
Lysosomal exocytosis
Two-pore channel
Agonist
Vesicle motility
TMAP
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Summary:[Display omitted] •Two novel agonists (TPC2-A1-N and TPC2-A1-P) activate two-pore channel 2 (TPC2) with distinct ion selectivities simulating gating of TPC2 by NAADP or PIP2.•The permeability coefficient (PCa/PNa) was about 0.65 for activation of TPC2 with TPC2-A1-N similar to PCa/PNa for NAADP and 0.04 for that with TPC2-A1-P, comparable to PCa/PNa for PIP2.•TPC2-A1-N can activate a TPC2-mediated increase of endo-lysosomal pH and impaired vesicle motility.•TPC2-A1-P can activate lysosomal exocytosis. TPC2-A1-N and TPC2-A1-P, two novel small molecules, differentially activate two-pore channel 2 (TPC2) and mimic the activation of TPC2 with NAADP and PIP2, resulting in distinct ion channel selectivities. These two different modes of TPC2 activity have physiological, and possibly pathophysiological, implications as they can modulate vesicle trafficking and lysosomal exocytosis.
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ISSN:0143-4160
1532-1991
DOI:10.1016/j.ceca.2020.102215