KB-R7943 is a plasma membrane Na(+)/Ca(2+) exchanger inhibitor. KB-R7943 reversibly inhibits inward and outward Na+/Ca2+ exchange in a dose-dependent manner (MCU; IC50 = 5.5 μM), but it does not affect Na+-dependent transport systems or ionotropic glutamate receptors. In addition, the effects of KB-R7943 on Ca(2+) homeostasis provide new evidence for the role of mitochondria modulating Ca(2+)-release and regenerative Ca(2+)-oscillations. KB-R7943 (10 and 30 microM) suppressed the tonotropic effect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX. KB-R7943 is also a potent blocker of the transient receptor potential channels (TRPC) TRPC3, TRPC5 and TRPC6.