New Role of Nicotinic Acid Adenine Dinucleotide Phosphate in Cardiac Arrhythmias♦

♦ See referenced article, J. Biol. Chem. 2013, 288, 16017–16030

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a strong second messenger for Ca²⁺ release. Preliminary studies suggested that NAADP played a role in cardiac signaling, but its role in cardiac arrhythmias was unknown. In this Paper of the Week, a team led by Andreas H. Guse at the University Medical Centre Hamburg-Eppendorf in Germany showed that the β-adrenergic agonist isoproterenol caused spontaneous and transient Ca²⁺ signaling in cardiac myocytes, causing cardiac arrhythmias in live mice. In in vitro studies, the investigators demonstrated that when they infused NAADP into intact cardiac myocytes, global Ca²⁺ signals were triggered that were inhibited by the NAADP antagonist BZ194. This compound also blocked spontaneous Ca²⁺ transient signals caused by high concentrations of isoproterenol. The authors say, “Our findings indicate a hitherto unappreciated pivotal role for NAADP in fine tuning of cardiac excitation-contraction coupling and open the way for novel therapeutic treatment of cardiac arrhythmias.”

Changes in calcium concentration in cardiac myocytes loaded with Fura-2/AM and subjected to combined Ca²⁺ imaging and intracellular infusion via a patch-clamp pipette.