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

Academic Article

Abstract

  • This paper examines relationships between trans-membrane potential (V(m)), [Ca 2+](i) dependent membrane ionic currents, and [Ca 2+](i) handling by the sarcoplasmic reticulum (SR) in a two-dimensional model of cardiac tissue. Luo-Rudy dynamic (LRd) membrane equations were used because they include detailed formulations for triggered SR Ca 2+ release dependent on membrane Ca 2+ influx (CICR) and for spontaneous SR Ca 2+ release following calsequestrin buffer 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 intervals of 320-350 ms, was preferential at sites located inside the functional center, and destabilized the reentrant activation sequence. Although adjustment of LRd parameters for SR Ca 2+ modified SCR interval and peak [Ca 2+](i) in voltage clamp simulations with a command waveform representing V(m) time course within the functional center, SCR persisted. Using the same command waveform, SCR also occurred with an alternate SR Ca 2+ formulation that represented subcellular details underlying CICR. LRd parameter adjustments to promote CICR and limit SCR in subsequent reentry simulations failed to eliminate SCR completely, as they modulated SCR intervals in a manner consistent with the voltage clamp simulations. Taken together, our findings support a destabilizing influence of functional reentry on [Ca 2+](i) handling. However, [Ca 2+](i) instabilities did not always fractionate depolarization wavefronts during reentry. Fractionation depended, in part, upon CICR and SCR parameters in the LRd formulation for SR Ca 2+ release.
  • Digital Object Identifier (doi)

    Author List

  • Pollard AE; Lit LM; Rogers JM
  • Start Page

  • 1228
  • End Page

  • 1236
  • Volume

  • 47
  • Issue

  • 9