It is known that both RyR2s and IP<sub>3</sub>R2s are expressed on the SR membrane of ventricular cardiomyocytes and that the expression of IP<sub>3</sub>R2s on the SR is increased in cardiac diseases such as heart failure (HF), and evidence that Ca<sup>2+</sup> release through IP<sub>3</sub>R2s can influence RyR2-mediated Ca<sup>2+</sup> release in excitation-contraction coupling has been described. The gene discussed is RYR2; the disease is heart failure.