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NAADP controls cross-talk between distinct Ca2+ stores in the heart.

Authors
  • Macgregor, Andrew
  • Yamasaki, Michiko
  • Rakovic, Stevan
  • Sanders, Luke
  • Parkesh, Raman
  • Churchill, Grant C
  • Galione, Antony
  • Terrar, Derek A
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publication Date
May 18, 2007
Volume
282
Issue
20
Pages
15302–15311
Identifiers
PMID: 17387177
Source
Medline
License
Unknown

Abstract

In cardiac muscle the sarcoplasmic reticulum (SR) plays a key role in the control of contraction, releasing Ca(2+) in response to Ca(2+) influx across the sarcolemma via voltage-gated Ca(2+) channels. Here we report evidence for an additional distinct Ca(2+) store and for actions of nicotinic acid adenine dinucleotide phosphate (NAADP) to mobilize Ca(2+) from this store, leading in turn to enhanced Ca(2+) loading of the SR. Photoreleased NAADP increased Ca(2+) transients accompanying stimulated action potentials in ventricular myocytes. The effects were prevented by bafilomycin A (an H(+)-ATPase inhibitor acting on acidic Ca(2+) stores), by desensitizing concentrations of NAADP, and by ryanodine and thapsigargin to suppress SR function. Bafilomycin A also suppressed staining of acidic stores with Lysotracker Red without affecting SR integrity. Cytosolic application of NAADP by means of its membrane permeant acetoxymethyl ester increased myocyte contraction and the frequency and amplitude of Ca(2+) sparks, and these effects were inhibited by bafilomycin A. Effects of NAADP were associated with an increase in SR Ca(2+) load and appeared to be regulated by beta-adrenoreceptor stimulation. The observations are consistent with a novel role for NAADP in cardiac muscle mediated by Ca(2+) release from bafilomycin-sensitive acidic stores, which in turn enhances SR Ca(2+) release by increasing SR Ca(2+) load.

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