The role of NAADP in maintaining spontaneous heart contractions: comparative physiological studies

Abstract

The goal of the work was to study the role of the second messenger NAADP (Nicotinic Acid Adenine Dinucleotide Phosphate), which causes the release of Ca2+ ions from lysosomes and endosomes, in the regulation of heart contractions. Isolated hearts of the grape snail Helix pomatia and a chicken embryo were used as models. Using the membrane-permeable acetooxymethyl ester NAADP-AM, we showed that NAADP at nanomolar concentrations increases the frequency and amplitude of spontaneous cardiac contractions in H. pomatia. The NAADP antagonist NED19, without affecting the amplitude of contractions, dose-dependently reduces their frequency, completely blocking spontaneous contractions of the mollusk heart at a concentration of 5 μM. The V-type H+-ATPase inhibitor bafilomycin A1 suppresses the accumulation of calcium ions in lysosomes and acidic endosomes. We have shown that bafilomycin A1 causes attenuation of spontaneous contractions and cardiac arrest in H. pomatia. Serotonin increases the amplitude of contractions of the H. pomatia heart without affecting heart rate. NED19 at saturating concentrations (10 μM) reduces the frequency of contractions when the snail heart is activated by serotonin, but only partially reduces their amplitude. In experiments with the isolated chick embryo heart, we showed that NED19 reduces the frequency of spontaneous contractions without affecting the amplitude of contractions. Based on the data obtained, a hypothesis was put forward that the release of calcium ions from lysosomes and endosomes under the influence of endogenous NAADP ensures the maintenance of spontaneous contractions of the heart.