Characterization of Intracellular Ca2+ Transient by the Hybrid Logistic Function in Aequorin-Injected Rabbit and Mouse Papillary Muscles

Abstract

Myocardial intracellular calcium (Ca2+) transients (CaTs) regulate tension generation and relaxation. Isometric tension curves are often analyzed using exponential equations; however, we previously demonstrated that hybrid logistic (HL) functions, which describe the difference between two S-shaped logistic functions, provide more accurate representations. In the present study, we investigated the potential application of HL functions for analyzing CaTs directly. CaTs were measured using the calcium-sensitive bioluminescent protein, aequorin, in 7 isolated rabbit right ventricular and 15 isolated mouse left ventricular papillary muscles. CaT data were fit by the least-squares method using HL and polynomial exponential (PE) function equations. The mean correlation coefficient (r) values of HL and PE fits were 0.9934 vs. 0.9523 in rabbit and 0.9980 vs. 0.9407 in mouse, respectively. The Z transformation of r value and the adjusted coefficient of determination (r squares) were higher, and the residual mean squares and Akaike information criterion values, which estimate goodness of fit between functions with different numbers of parameters, were lower for the HL curves than for the PE curves in both rabbit and mouse. There were significant correlations between the calculated values from the best-fit HL function curve and the primary CaT data. Thus the HL function curves more accurately described the amplitudes and time courses of CaTs in both rabbit and mouse papillary muscles. We speculate that the first logistic component curve reflects the concentration and time course of Ca2+ inflow into the cytoplasmic space, and that the second logistic component curve reflects the concentrations and time courses of Ca2+ removal from the cytoplasmic space as well as Ca2+ binding to troponin. This approach might provide a more robust model for studying CaTs and cardiac cycle regulation.