A mechanism for myocardial uptake of /sup 201/Tl

Although the kinetics of Tl have been studied extensively the mechanisms governing its intracellular distribution in myocardium are not fully understood. One possibility is that Tl distributes within the interstitial and intracellular spaces according to the electrochemical gradients established by the cell membrane potential (ΔPSI). If so, the equilibrium concentrations C/sub I/ (intracellular) and C/sub O/ (interstitial) will obey the second law of thermodynamics as expressed by the Nernst Equations. To test this hypothesis the authors used a preparation of beating fetal mouse hearts in an organ culture medium. The measured concentration ratio (mouse heat to medium), R, was measured as a function of time and was fit to the model R=0.323[1+(K/sub I//K/sub O/)(1-EXP(-K/sub O/t)], where K/sub I/ and K/sub O/ are the inward and outward rate constants for transport across the cell membrane. At equilibrium, conservation of tracer mass ensures that C/sub I//C/sub O/=0.323 K/sub I//K/sub O/, where 0.323 is the ratio of interstitial to intracellular volume. In the control state the model estimate of the equilibrium membrane potential was -87 mV; whereas, for graded tissue injury the magnitude of the membrane potential decreased in proportion to the severity of injury. These data, obtained without the confounding effect of blood flow, show that intracellular Tl uptake in the fetal mouse heart can be interpreted in terms of membrane potential. The results of this work can in principle be extended to the use of radiolabeled molecules and ECT for in vivo measurement of regional membrane potential