P12 - Control of neuronal and cardiac function by two-pore channels
Two-pore channels (TPC1 and TPC2) are novel members of the TRP channel superfamily that display specific localization in endolysosomal organelles. Upon activation by agonists such as nicotinic acid adenine dinucleotide phosphate (NAADP) and the phosphoinositide PI(3,5)P2, TPCs confer intracellular Ca2+ release that is involved in multiple signaling pathways. Besides their role in intracellular signaling TPCs were supposed to be involved in fusion and trafficking of endolysosomal organelles. Using mouse lines deficient for the two TPCs we will examine to which extent principal TPC roles affect cardiac and hippocampal function.
Figure. Potential roles of TPCs in cardiac function. Ca2+ signals arising from TPC activation in endo-lysosomal organells have been proposed to contribute to pacemaking in sinoatrial node (SAN) cells as well as in cardiac EC coupling. Pathologically, TPCs may be involved in the generation of spontaneous Ca2+ transients (SCTs) during catecholamine-induced arrhythmia.