Heterozygous RyR2 Ex3-del mutant mice with cardiac specific, conditional KO of the WT RyR2 allele exhibit bradycardia, but no CPVT.

<p>iRyR2^flox/flox (n = 11) and iRyR2^flox/Ex3-del (n = 8) mice were treated with tamoxifen. ECG recording was performed 12 days post tamoxifen treatment to determine their basal heart rates (before epinephrine/caffeine challenge) (A) and their susceptibility to CPVT (B, C). Representative ECG recordings of the tamoxifen-treated iRyR2^flox/flox mice (B) and the tamoxifen-treated iRyR2^flox/Ex3-del mice (C) before (top panel) and after (bottom panel) the injection of epinephrine (1.6 mg/kg) and caffeine (120 mg/kg). Note that no VTs were detected in either the tamoxifen-treated iRyR2^flox/flox mice (B) or the tamoxifen-treated iRyR2^flox/Ex3-del mice during the 30-min period of ECG recording after the injection of the triggers (*P<0.05).