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Updated: Jun 22, 2026

Patch-Clamp Techniques for Single Endolysosomal Vesicle Analysis
Published on: April 4, 2025
The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels
Antony Galione1, A Mark Evans, Jianjie Ma
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. antony.galione@pharm.ox.ac.uk
Abstract:
In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca(2+) mobilisation. In addition, we describe how TPCs may also trigger further Ca(2+) release by coupling to the endoplasmic reticular stores through activation of IP(3) receptors and ryanodine receptors.
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