From these observations showing that NAADP and TPC2 appear to participate in the effects of the β-adrenoreceptor agonist isoproterenol to increase the amplitude of Ca2+ transients in electrically stimulated myocytes, and taking into account the finding that arrhythmias caused by isoproterenol could be suppressed by the NAADP antagonist BZ194 (34), we hypothesized that isoproterenol-mediated increases in NAADP acting via TPC2 proteins might also be involved in the susceptibility to cardiac arrhythmias in the intact heart. This evidence concerns the gene TPCN2 and cardiac rhythm disease.