Carvedilol analogue, VK-II-36. A, Chemical structures of carvedilol and VK-II-36. B, Fura-2 ratios of a representative RyR2-R4496C expressing HEK293 cell perfused with KRH buffer containing 1 mM extracellular Ca2+ and increasing dose of VK-II-36 followed by the addition of 10 mM caffeine. Note that VK-II-36 dose-dependently inhibited spontaneous Cai oscillations (i.e. SOICR) in HEK293 cells. C, The fraction of HEK293 cells that display spontaneous Cai oscillations in the presence of various concentration of VK-II-36 (white circles, n = 403) or DMSO (black circles, n=10). P < 0.01.