NAADP influences excitation-contraction coupling by releasing calcium from lysosomes in atrial myocytes
Collins TP., Bayliss R., Churchill GC., Galione A., Terrar DA.
In atrial myocytes, the sarcoplasmic reticulum (SR) has an essential role in regulating the force of contraction as a consequence of its involvement in excitation-contraction coupling (ECC). Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ mobilizing messenger that acts to release Ca2+ from an acidic store in mammalian cells. The photorelease of NAADP in atrial myocytes increased Ca2+ transient amplitude with no effect on accompanying action potentials or the L-type Ca2+ current. NAADP-AM, a cell permeant form of NAADP, increased Ca2+ spark amplitude and frequency. The effect on Ca2+ spark frequency could be prevented by bafilomycin A1, a vacuolar H+-ATPase inhibitor, or by disruption of lysosomes by GPN. Bafilomycin prevented staining of acidic stores with LysoTracker red by increasing lysosomal pH. NAADP-AM also produced an increase in the lysosomal pH, as detected by a reduction in LysoSensor green fluorescence. These effects of NAADP were associated with an increase in the amount of caffeine-releasable Ca2+ in the SR and may be regulated by β-adrenoceptor stimulation with isoprenaline. These observations are consistent with a role for NAADP in regulating ECC in atrial myocytes by releasing Ca2+ from an acidic store, which enhances SR Ca2+ release by increasing SR load. © 2011 Elsevier Ltd.