Underlying mechanisms of symmetric calcium wave propagation in rat ventricular myocytes

Calcium waves in heart cells are mediated by diffusion-coupled calcium-indu ced calcium release. The waves propagate in circular fashion. This is count erintuitive in view of the accepted ultrastructure of the cardiac myocyte, The density of calcium release sites in the transverse direction is four ti mes higher than in the longitudinal direction. Simulations with release sit es localized along Z-lines and isotropic diffusion yielded highly elliptica l, nonphysiological waves. We hypothesized that subcellular organelles coun teracted the higher release site density along the Z-lines by acting as tra nsverse diffusion barriers and sites of active calcium uptake. We quantifie d the reduction of transverse diffusion by microinjecting cells with the no nreactive dye fluorescein. The ratio of the radial diffusion coefficient to the longitudinal coefficient was 0.39, Inhibition of mitochondrial uptake by rotenone accelerated the wave in the transverse direction. Simulations w ith release sites clustered at the Z-lines and a transverse diffusion coeff icient 50% of the longitudinal coefficient generated waves of ellipticity 2 /1 (major axis along the Z-line), Introducing additional release sites betw een the Z-lines at a density 20% of that on the Z-lines produced circular w aves, The experiments and simulations support the presence of transverse di ffusion barriers, additional uptake sites, and possibly intermediate releas e sites as well.