The acid test: The discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca2+ release channels

Antony Galione, A. Mark Evans, Jianjie Ma, John Parrington, Abdelilah Arredouani, Xiaotong Cheng, Michael X. Zhu

Research output: Contribution to journalArticle

61 Citations (Scopus)


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 Ca2+ mobilisation. In addition, we describe how TPCs may also trigger further Ca2+ release by coupling to the endoplasmic reticular stores through activation of IP3 receptors and ryanodine receptors.

Original languageEnglish
Pages (from-to)869-876
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Issue number5
Publication statusPublished - 1 Sep 2009



  • Ca2+ mobilisation
  • Ca2+ stores
  • Ca2+-induced Ca2+ release
  • Calcium signalling
  • Calcium transient
  • Cholecystokinin
  • Endothelin
  • Inositol 1,4,5-trisphosphate
  • Ion channel
  • Pancreatic β-cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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