Role of Ca2+ mobilizing second messenger NAADP in local and global Ca2+ signalling in mouse cardiac myocytes

• Applicant: Professor Dr. Andreas H. Guse
• Subject Area: Pharmacology
• Term: from 2005 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13286686

Ca2+ signaling is the central signaling pathway in cardiac myocytes that intracellularly transmits excitation-contraction coupling. Cardiac ryanodine receptors play a pivotal role in this process. The endogenous adenine nucleotides cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) serve as second messengers and/or modulators of ryanodine receptors, while another endogenous adenine nucleotide, adenosine diphosphoribose (ADPR) activates the transient receptor potential M2 (TRPM2) cation channel. Though the role of these nucleotides is clear in some cell types, their precise role in heart remains largely unknown. Thus, the scientific goals of this project are the analysis of the (i) cADPR/Ca2+ signaling pathway, (ii) the NAADP/Ca2+ signaling pathway, and (iii) the ADPR/TRPM2/Ca2+ signaling pathway in cardiac myocytes. Mass analysis of these endogenous adenine nucleotides as well as single cell Ca2+ imaging studies, partially combined with microinjection will be used to achieve these goals. The development of membran-permeant analogues of the endogenous adenine nucleotides may in addition result in novel lead structures for pharmaceutical drugs.

• DFG Programme: Research Units
• Subproject of: FOR 604: Signalling Pathways in the Healthy and Diseased Heart
• Participating Person: Dr. Cornelia Siebrands