An Improved Model of Ba Current through L-type Ca Channels Including Voltage- and Ion-Dependent Inactivation

The substitution of Ba ions for Ca has been widely used to separate voltage-dependent inactivation (VDI) from Ca-dependent inactivation (CDI) of the Ca current (ICa) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (IBa) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes IBa inactivation as VDI only, into the Shannon et al. excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental IBa inactivation could be recapitulated by modifying CDI. Simulation results show that IBa inactivation measured in rabbit myocytes at physiological temperature can be recapitulated when making the Ca-dependent transition rates 10-fold less sensitive to Ba vs. Ca. Our extended LTCC model provides a more faithful representation of purely VDI during ICa.