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Exploring the biophysical evidence that mammalian two‐pore channels are NAADP‐activated calcium‐permeable channels
Author(s) -
Pitt Samantha J.,
ReillyO'Donnell Benedict,
Sitsapesan Rebecca
Publication year - 2016
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270936
Subject(s) - cytosol , biophysics , gating , intracellular , ion channel , chemistry , biochemistry , calcium , microbiology and biotechnology , biology , enzyme , receptor , organic chemistry
Nicotinic acid adenine dinucleotide phosphate (NAADP) potently releases Ca 2+ from acidic intracellular endolysosomal Ca 2+ stores. It is widely accepted that two types of two‐pore channels, termed TPC1 and TPC2, are responsible for the NAADP‐mediated Ca 2+ 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 Ca 2+ . 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 Ca 2+ over K + than TPC1 and hence capable of releasing greater quantities of Ca 2+ 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 Ca 2+ ‐release channels of the endolysosomal system.