Fan Junjie, Yu Zeyun
Department of Computer Science, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:4499-503. doi: 10.1109/IEMBS.2009.5333685.
Local calcium sparks in the dyadic cleft of cardiac myocytes are triggered by calcium influxes via L-type calcium channels (LCCs) located on the transverse tubule (TT) membrane, and subsequently controlled by the regeneration of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR). Calcium released from SR channels is known to be responsible for the sparks. Therefore, the activities of RyRs provide straightforward indication to the calcium concentration alteration. A method to study calcium signaling by analyzing RyR-gating statistics is described in the present study. Here we propose a univariate model with a simplified geometry of the dyadic cleft, which specifies the spatial localization of LCCs and RyRs to monitor the activity changes of RyRs. This model is used to explore two crucial aspects of local calcium signaling: the first is to disclose the tight control of calcium influxes via LCCs, and the second is to reveal the interactional impact of the self-regenerative RyRs. Patterns of active RyRs are rendered through numerous computational simulation experiments, manipulating the state initialization and the spatial localization of LCCs and RyRs to observe gating transition of RyRs.
心肌细胞二联体裂隙处的局部钙火花由通过位于横管（TT）膜上的L型钙通道（LCCs）的钙内流触发，随后由肌浆网（SR）上的兰尼碱受体（RyRs）的再生控制。已知从SR通道释放的钙是产生钙火花的原因。因此，RyRs的活性为钙浓度变化提供了直接指示。本研究描述了一种通过分析RyR门控统计来研究钙信号传导的方法。在这里，我们提出了一个具有简化二联体裂隙几何结构的单变量模型，该模型指定了LCCs和RyRs的空间定位，以监测RyRs的活性变化。该模型用于探索局部钙信号传导的两个关键方面：第一个是揭示通过LCCs对钙内流的严格控制，第二个是揭示自再生RyRs的相互作用影响。通过大量的计算模拟实验呈现活跃RyRs的模式，操纵LCCs和RyRs的状态初始化和空间定位，以观察RyRs的门控转变。
