KINETICS OF [CA](I) DECLINE IN CARDIAC MYOCYTES DEPEND ON PEAK [CA](I)

The rate of decline of free intracellular Ca concentration ([Ca](i)) i s a potentially useful index of the function of Ca transport systems. However, interpretations of these results may depend on multiple Ca tr ansport systems and interaction with intracellular Ca binding sites. W e measured [Ca](i) in voltage-clamped ventricular myocytes isolated fr om rat hearts using indo 1 fluorescence. Conditions were chosen where [Ca](i) decline was expected to depend almost exclusively on the sarco plasmic reticulum Ca pump. The half time of [Ca](i) decline (t(1/2)) d ecreased as the amplitude of the intracellular Ca (Ca-i) transient inc reased. This is not the result that would be expected from a transport system where the transport rate is a linear function of free [Ca](i). In this case the time constant of [Ca](i) decline (tau) should be ind ependent of the peak value of [Ca](i). This is also true if linear buf fering of Ca-i is included. We develop a simple but more realistic the oretical framework where Ca transport rate and Ca binding both depend on free [Ca](i) with Michaelis-Menten type functions. We demonstrate t hat the observed decline in apparent tau with increasing peak [Ca](i) is entirely expected on theoretical grounds and over a wide range of c haracteristics for Ca transport and binding. We conclude that one cann ot draw inferences about the intrinsic Ca transport function based on tau values unless the Cai transient has a comparable size.