An Improved Model of Ba Current throught 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 (I-Ca) through L-type Ca channels (LTCCs). However, a modest ion-dependent inactivation of Ba current (I-Ba) has been shown experimentally. We have incorporated the Mahajan et al. Markov model of LTCC, which describes I-Ba inactivation as VDI only, into the Shannon et al. excitation-contraction coupling model. We extended the LTCC model to assess whether and how experimental I-Ba inactivation could be recapitulated by modifying CDI. Simulation results show that I-Ba 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 I-Ca.