The effect of heterogeneously-distributed RyR channels on calcium dynamics in cardiac myocytes.
Calcium plays an essential role in excitation-contraction coupling in muscle, and derangements in calcium handling can produce a variety of potentially harmful conditions, especially in cardiac muscle. In cardiac tissue specialized invaginations of the sarcolemma, called T-tubules, penetrate deep into each sarcomere, and depolarization of the SL leads to an influx of calcium through voltage-sensitive channels in the T-tubules that in turn triggers further calcium release from the sarcoplasmic reticulum via ryanodine-sensitive calcium channels. Under certain conditions, such as elevated external Ca2+, cardiac cells can release calcium from the sarcoplasmic reticulum spontaneously, producing a calcium 'spark' and propagating traveling waves of elevated Ca2+ concentration, without depolarization of the SL (Wier and Blatter, 1991a, Cell Calcium 12, 241-254; Williams, 1993, Cell Calcium 14, 724-735; Cheng et al., 1993a, Science 262, 740-744). However, under normal resting conditions these potentially harmful waves seldom occur. In this paper we investigate the role of the periodic distribution of ryanodine-sensitive channels in determining whether a spark can trigger a wave, using a modification of the kinetic model proposed by Tang and Othmer, 1994b, Biophys. J. 67, 2223-2235, for calcium-induced calcium release. We show that the spatial localization of these channels near the T-tubules has a significant effect on both wave propagation and the onset of oscillations in this system. Spatial localization provides a possible explanation for the differing effects of various experimental protocols on the system's ability to propagate a traveling wave.
Spiro
P A
PA
Department of Mathematics, University of Utah, Salt Lake City, UT 84112, USA.
Othmer
H G
HG
D000818:Animals; D020013:Calcium Signaling; D008433:Mathematics; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel