The rate- and species-dependence of short-term memory in cardiac myocytes

Short-term memory is an intrinsic property of paced cardiac myocytes that reflects the influence of pacing history, and not just the immediately preceding diastolic interval (DI), on the action potential duration (APD). Although it is recognized that short-term memory affects the dynamics of cardiac myocytes in general, and the onset of irregular cardiac rhythm in particular, its has never been adequately quantified or measured directly in experiments or numerical simulations, mainly due to the absence of appropriate techniques. As a result, very little is known about the rate- and species dependent behavior of short-term memory. In this study, we introduce a new approach that allows one to estimate how much short-term memory, M(S), is present in the cardiac myocyte at different pacing rates. The new quantification is based on the fact that pacing history affects not only the APD, but the entire dynamics of paced cardiac myocytes, in particular the restitution curve. Using the patch clamp technique and numerical simulations, we measured short-term memory restitution-the dependence of M(S) on the cycle length-in isolated rabbit and guinea pig ventricular myocytes. In both species, M(S) is rate- and species-dependent, displaying a biphasic behavior as a function of cycle length. Moreover, our results indicate that there is a significant difference in M(S) measured between both species at small cycle lengths. Numerical simulations suggest that the kinetics of the rapidly activating delayed rectifier potassium current I(Kr) is partially responsible for this difference.