Functional reentry's influence on intracellular calcium in the LRd membrane equations

This paper examines relationships between transmembrane potential(V-m), [Ca 2+](i) dependent membrane ionic currents, and [Ca2+](i) handling by the sar coplasmic reticulum (SR) in a two-dimensional model of cardiac tissue. Luo- Rudy dynamic (LRd) membrane equations were used because they include detail ed formulations for triggered SR Ca2+ release dependent on membrane Ca2+ in flux (CICR) and for spontaneous SR Ca2+ release following calsequestrin buf fer overload (SCR). Reentry's rapid rate (110-ms cycle length) elevated [Ca 2+](i) and limited CICR, which in turn promoted SCR that occurred at inter c-als of 320-350 ms, was preferential at sites located inside the functiona l center, and destabilized the reentrant activation sequence, Although adju stment of LRd parameters for SR Ca2+ modified SCR interval and peak [Ca2+]( i) in voltage clamp simulations with a command waveform representing V-m ti me course within the functional center, SCR persisted. Using the same comma nd waveform, SCR also occurred with an alternate SR Ca2+ formulation that r epresented subcellular details underlying CICR, LRd parameter adjustments t o promote CICR and limit SCR in subsequent reentry simulations failed to el iminate SCR completely, as they modulated SCR intervals in a manner consist ent with the voltage clamp simulations. Taken together, our findings suppor t a destabilizing influence of functional reentry on [Ca2+](i) handling. Ho wever, [Ca2+](i) instabilities did not always fractionate depolarization wa vefronts during reentry. Fractionation depended, in Dart, upon CICR and SCR parameters in the LRd formulation for SR Ca2+ release.