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

Journal article

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 Ca 2+ mobilizing messenger that acts to release Ca 2+ from an acidic store in mammalian cells. The photorelease of NAADP in atrial myocytes increased Ca 2+ transient amplitude with no effect on accompanying action potentials or the L-type Ca 2+ current. NAADP-AM, a cell permeant form of NAADP, increased Ca 2+ spark amplitude and frequency. The effect on Ca 2+ 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 Ca 2+ 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 Ca 2+ from an acidic store, which enhances SR Ca 2+ release by increasing SR load. © 2011 Elsevier Ltd.

Authors: Collins, T; Bayliss, R; Churchill, G; Galione, A; Terrar, D

• Journal: Cell Calcium
• Volume: 50
• Issue: 5
• Pages: 449-458
• Publication date: 2011-11-01
• DOI: 10.1016/j.ceca.2011.07.007
• EISSN: 1532-1991
• ISSN: 0143-4160
• Language: English
• Keywords: NAADP; Atrial myocytes; Calcium; Lysosomes