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The effect of heterogeneously-distributed RyR channels on calcium dynamics in cardiac myocytes

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Abstract

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.

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  1. Peter A. Spiro

    Present address: Incyte Pharmaceuticals Inc., 3174 Porter Drive, Palo Alto, CA, 94304, USA

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  1. Department of Mathematics, University of Utah, Salt Lake City, UT, 84112, USA

    Peter A. Spiro & Hans G. Othmer

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Supported in part by NIH Grant GM29123.

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Spiro, P.A., Othmer, H.G. The effect of heterogeneously-distributed RyR channels on calcium dynamics in cardiac myocytes. Bull. Math. Biol. 61, 651–681 (1999). https://doi.org/10.1006/bulm.1999.0101

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