P124NAADP as a novel downstream mediator of cardiac beta-adrenergic pathway.
Lin W., Bolton E., Capel R., Wang Y., Galione A., Terrar DA.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent endogenous Ca2+ mobilizing second messenger that is known to release Ca2+ from the acidic endolysosomal vesicles. Our previous work showed that intracellular application of NAADP led to the increase in contractions of electrically stimulated guinea pig ventricular cardiomyocytes. These observations were accompanied by an increase in sarcoplasmic reticulum (SR) Ca2+ load. Previously, it has been reported that beta-adrenergic activation increases the level of NAADP in guinea pig whole heart experiments, and we therefore hypothesized that the inotropic effect of beta-adrenergic activation is partly mediated by NAADP. This study aims to test this possibility and subsequently dissect the related pathway.