title: NAADP influences excitation-contraction coupling by releasing calcium from lysosomes in atrial myocytes.
abstract: 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.
authors: Department of Pharmacology, University of Oxford, Mansfield Road, UK. thomaspetercollins@gmail.com
authors: Thomas P
authors: TP
authors: Collins
authors: Rebecca
authors: R
authors: Bayliss
authors: Grant C
authors: GC
authors: Churchill
authors: Antony
authors: A
authors: Galione
authors: Derek A
authors: DA
authors: Terrar
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054849:Cardiac Electrophysiology; D056966:Excitation Contraction Coupling; D006168:Guinea Pigs; D006325:Heart Atria / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D000318:Adrenergic beta-Agonists; D009249:NADP; C024376:NAADP; D002118:Calcium