Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.
Lysosome
Small-molecule activator
Small-molecule inhibitor
TPC
TRPML
Journal
Handbook of experimental pharmacology
ISSN: 0171-2004
Titre abrégé: Handb Exp Pharmacol
Pays: Germany
ID NLM: 7902231
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
28
4
2023
pubmed:
29
7
2022
entrez:
28
7
2022
Statut:
ppublish
Résumé
Functional characterization of endolysosomal ion channels is challenging due to their intracellular location. With recent advances in endolysosomal patch clamp technology, it has become possible to directly measure ion channel currents across endolysosomal membranes. Members of the transient receptor potential (TRP) cation channel family, namely the endolysosomal TRPML channels (TRPML1-3), also called mucolipins, as well as the distantly related two-pore channels (TPCs) have recently been characterized in more detail with endolysosomal patch clamp techniques. However, answers to many physiological questions require work in intact cells or animal models. One major obstacle thereby is that the known endogenous ligands of TRPMLs and TPCs are anionic in nature and thus impermeable for cell membranes. Microinjection, on the other hand, is technically demanding. There is also a risk of losing essential co-factors for channel activation or inhibition in isolated preparations. Therefore, lipophilic, membrane-permeable small-molecule activators and inhibitors for TRPMLs and TPCs are urgently needed. Here, we describe and discuss the currently available small-molecule modulators of TRPMLs and TPCs.
Identifiants
pubmed: 35902436
doi: 10.1007/164_2022_605
doi:
Substances chimiques
Transient Receptor Potential Channels
0
Cations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-276Informations de copyright
© 2022. Springer Nature Switzerland AG.
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