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Biophys J, January 2001, p. 1-11, Vol. 80, No. 1


and
*Department of Chemical Engineering, Texas Tech University,
Lubbock, Texas 79409, and
Department of Physiology,
Texas Tech University Health Science Center, Lubbock, Texas
79430 USA
Calcium waves in heart cells are mediated by
diffusion-coupled calcium-induced calcium release. The waves propagate
in circular fashion. This is counterintuitive in view of the accepted
ultrastructure of the cardiac myocyte. The density of calcium release
sites in the transverse direction is four times higher than in the
longitudinal direction. Simulations with release sites localized along
Z-lines and isotropic diffusion yielded highly elliptical,
nonphysiological waves. We hypothesized that subcellular organelles
counteracted the higher release site density along the Z-lines by
acting as transverse diffusion barriers and sites of active calcium
uptake. We quantified the reduction of transverse diffusion by
microinjecting cells with the nonreactive 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 with release sites clustered at the Z-lines and a transverse diffusion coefficient 50% of
the longitudinal coefficient generated waves of ellipticity 2/1 (major
axis along the Z-line). Introducing additional release sites between
the Z-lines at a density 20% of that on the Z-lines produced circular
waves. The experiments and simulations support the presence of
transverse diffusion barriers, additional uptake sites, and possibly
intermediate release sites as well.
Biophys J, January 2001, p. 1-11, Vol. 80, No. 1
© 2001 by the Biophysical Society 0006-3495/01/01/01/11 $2.00
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