Exploring the biophysical evidence that mammalian two pore channels are NAADP-activated calcium-permeable channels
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Nicotinic acid adenine dinucleotide phosphate (NAADP) potently releases Ca2+ from acidic intracellular endo-lysosomal Ca2+-stores. It is widely accepted that two types of two pore channels, termed TPC1 and TPC2, are responsible for the NAADP-mediated Ca2+-release but the underlying mechanisms regulating their gating appear to be different. For example, although both TPC1 and TPC2 are activated by NAADP, TPC1 appears to be additionally regulated by cytosolic Ca2+. Ion conduction and permeability also differ markedly. TPC1 and TPC2 are permeable to a range of cations although biophysical experiments suggest that TPC2 is slightly more selective for Ca2+ over K+ than TPC1 and hence capable of releasing greater quantities of Ca2+ from acidic stores. TPC1 is also permeable to H+ and therefore may play a role in regulating lysosomal and cytosolic pH, possibly creating localised acidic domains. The significantly different gating and ion conducting properties of TPC1 and TPC2 suggest that these two ion channels may play complementary physiological roles as Ca2+ release channels of the endo-lysosomal system.
Pitt , S J , Reilly O'Donnell , B & Sitsapesan , R 2016 , ' Exploring the biophysical evidence that mammalian two pore channels are NAADP-activated calcium-permeable channels ' The Journal of Physiology , vol 594 , no. 15 , pp. 4171-4179 . DOI: 10.1113/JP270936
The Journal of Physiology
© 2016, Publisher / the Author(s). This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at onlinelibrary.wiley.com / https://dx.doi.org/10.1113/JP270936
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