Evolution of cardiac calcium waves from stochastic calcium sparks

Leighton T Izu, W. Gil Wier, C. William Balke

Research output: Contribution to journalArticle

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Abstract

We present a model that provides a unified framework for studying Ca2+ sparks and Ca2+ waves in cardiac cells. The model is novel in combining 1) use of large currents (∼20 pA) through the Ca2+ release units (CRUs) of the sarcoplasmic reticulum (SR); 2) stochastic Ca2+ release (or firing) of CRUs; 3) discrete, asymmetric distribution of CRUs along the longitudinal (separation distance of 2 μm) and transverse (separated by 0.4-0.8 μm) directions of the cell; and 4) anisotropic diffusion of Ca2+ and fluorescent indicator to study the evolution of Ca2+ waves from Ca2+ sparks. The model mimics the important features of Ca2+ sparks and Ca2+ waves in terms of the spontaneous spark rate, the Ca2+ wave velocity, and the pattern of wave propagation. Importantly, these features are reproduced when using experimentally measured values for the CRU Ca2+ sensitivity (∼15 μM). Stochastic control of CRU firing is important because it imposes constraints on the Ca2+ sensitivity of the CRU. Even with moderate (∼5 μM) Ca2+ sensitivity the very high spontaneous spark rate triggers numerous Ca2+ waves. In contrast, a single Ca2+ wave with arbitrarily large velocity can exist in a deterministic model when the CRU Ca2+ sensitivity is sufficiently high. The combination of low CRU Ca2+ sensitivity (∼15 μM), high cytosolic Ca2+ buffering capacity, and the spatial separation of CRUs help control the inherent instability of SR Ca2+ release. This allows Ca2+ waves to form and propagate given a sufficiently large initiation region, but prevents a single spark or a small group of sparks from triggering a wave.

Original languageEnglish (US)
Pages (from-to)103-120
Number of pages18
JournalBiophysical Journal
Volume80
Issue number1
StatePublished - 2001
Externally publishedYes

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Calcium Signaling
Sarcoplasmic Reticulum
Direction compound

ASJC Scopus subject areas

  • Biophysics

Cite this

Evolution of cardiac calcium waves from stochastic calcium sparks. / Izu, Leighton T; Wier, W. Gil; Balke, C. William.

In: Biophysical Journal, Vol. 80, No. 1, 2001, p. 103-120.

Research output: Contribution to journalArticle

Izu, LT, Wier, WG & Balke, CW 2001, 'Evolution of cardiac calcium waves from stochastic calcium sparks', Biophysical Journal, vol. 80, no. 1, pp. 103-120.
Izu, Leighton T ; Wier, W. Gil ; Balke, C. William. / Evolution of cardiac calcium waves from stochastic calcium sparks. In: Biophysical Journal. 2001 ; Vol. 80, No. 1. pp. 103-120.
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