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Local character of calcium release in cardiac myocytes implies independent recruitment of calcium release units by triggering stimuli. Calcium release from individual CRUs also displays quantal character, interpreted either as recruitment of small cohorts of independent RYRs (1,2), or as recruitment of small cohorts of RYR clusters with coupled RYRs gating (3). We tested both interpretations on published experimental data using a model of virtual calcium release units (vCRUs) consisting of 1-10 clusters that were constructed in accordance with the experimentally observed cluster size distribution (4). If RYR gating was independent, vCRUs consisting of 3 or more clusters provided a good agreement between the model and experimental data (1). If RYR gating was coupled, the calcium release flux of vCRUs did not display quantal structure that would correspond to in situ observations. The model of RYR gating (2) combined with the model of independent RYRs in vCRUs (2) matched the experimentally observed calcium dependence of calcium spark frequency (5) under all conditions. However, the Mg2+-binding parameters of RYRs were in accordance with the single-channel observations (6) only for vCRUs composed of 3 or more clusters. In conclusion, these results favor independent over fully coupled RYR gating in situ, and predict the presence of at least 40 RYRs per cardiac calcium release unit.Supported by grants APVV-0441-09, APVV-0721-10, VEGA 2/0190/10, 2/0203/11, and 2/0197/11.References1. Wang SQ et al., PNAS 101: 3979-3984, 20042. Zahradnikova A et al., J. Gen. Physiol. 136: 101-116, 20103. Xie W et al., J. Gen. Physiol. 136: 129-133, 20104. Baddeley D et al., PNAS 106: 22275-22280, 20095. Lukyanenko V, Gyorke S, J Physiol. 521: 575-585, 19996. Zahradnikova A et al., Am J Physiol. 285, C1059-1070, 2003 |
