Modeling of the inactivation process of L-type Ca²⁺ channel

Abstract

Inactivation of the L-type Ca²⁺ channel regulates the amount of Ca²⁺ influx into cardiac myocytes. The inactivation can be driven not only by depolarization (voltage-dependent inactivation, VDI) but Ca²⁺ flow itself (Ca²⁺-dependent inactivation, CDI). Until now, the study of the modeling for these inactivation processes of the L-type Ca²⁺ channel has not been fully studied. In this study, we have modeled the VDI at first, and then the CDI was estimated to fit the channel current using Ca²⁺ as the charge carrier. To estimate the gating of VDI with minimizing the effect of CDI, we used measured the outward-going K⁺ current flowing through the Ca²⁺ channel in the absence of extracellular Ca²⁺ (Findlay I, J. Physiol. 2002). Thus, estimated VDI showed a biphasic decay, and were composed of fast, slow and steasy-state components. The VDI model composed of three components was developed to fit the time- and voltage-dependent behavior of each. Using the developed model, Ba²⁺ inward currents flowing through Ca²⁺ channel at various potentials were calculated with taking the surface charge into account. The simulated currents were in good agreement with the experimental results. Next, to develop CDI model, we added another inactivation parameter to fit the experimental Ca²⁺ current. In this attempt, we found it necessary to incorporate voltage-dependent nature of CDI. In conclusion, we have developed a reasonable model of Ca²⁺ channel inactivation, which may facilitate further experimental researches. [Jpn J Physiol 55 Suppl:S135 (2005)]