Theoretical investigation of the mechanism of heart failure using a canine ventricular cell model: Especially the role of up-regulated CaMKII and SR Ca2Â + leak

► Acute role of CaMKII does not contribute to APD prolongation for canine in HF. ► Enhanced INaL only partially contributes to [Na+] elevation in HF. ► The important role of enhanced Ileak on disturbed Ca2+ handling in HF is identified. ► Steeper fractional SR Ca2+ release in HF increases the susceptibility to alternans.