NAADP influences excitation–contraction coupling by releasing calcium from lysosomes in atrial myocytes

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.

► Nicotinic acid adenine dinucleotide phosphate (NAADP) releases Ca2+ from acidic stores.
► In cardiac atrial myocytes, photorelease of NAADP increased Ca2+ transient amplitude.
► A cell permeant form of NAADP increased Ca2+ spark amplitude and frequency.
► Effects of NAADP were associated with an increase in the amount of caffeine-releasable Ca2+ in the SR.
► The effects were prevented bafilomycin A1, a vacuolar H+-ATPase inhibitor.