The Role of NAADP in Maintaining Spontaneous Heart Contractions: Comparative Physiological Studies

• Published in: Moscow University biological sciences bulletin Vol. 79; no. Suppl 1; pp. S59 - S67
• Main Authors: Kuzmina, E. S., Nechaeva, M. V., Avdonin, P. V.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2024; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Calcium phosphates; Cell Biology; Endosomes; H+-transporting ATPase; Heart rate; Ions; Life Sciences; Lysosomes; NAADP; Nicotinic acid; Plant Sciences; Research Article; Serotonin; Zoology; chicken embryo; calcium; NAADP; heart contraction
• ISSN: 0096-3925; 1934-791X
• DOI: 10.3103/S0096392524600789

The work was aimed at studying the role of the second messenger NAADP (Nicotinic Acid Adenine Dinucleotide Phosphate), which causes the release of Ca
2+
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, the authors showed that the nanomolar concentrations of NAADP increase the frequency and amplitude of spontaneous cardiac contractions in
H. pomatia
. The NAADP antagonist, NED19, dose-dependently reduces their frequency, completely blocking spontaneous contractions of the mollusk heart at a concentration of 5 μM without affecting the amplitude of contractions. The V-type H
+
-ATPase inhibitor bafilomycin A1 suppresses the accumulation of calcium ions in lysosomes and acidic endosomes. It has been 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. The experiments with the isolated chick embryo heart showed that NED19 reduces the heart rate without affecting the amplitude of contractions. Based on the obtained data, 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.