Das Phonindra Nath, Mehrotra Parul, Mishra Aseem, Bairagi Nandadulal, Chatterjee Samrat
Centre for Mathematical Biology and Ecology, Department of Mathematics, Jadavpur University, Kolkata-700032, India; International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
Math Biosci. 2017 Jul;289:51-68. doi: 10.1016/j.mbs.2017.04.007. Epub 2017 Apr 27.
Calcium ions aid in the generation of action potential in myocytes and are responsible for the excitation-contraction coupling of heart. The heart muscle has specialized patches of cells, called excitatory cells (EC) such as the Sino-atrial node cells capable of auto-generation of action potential and cells which receive signals from the excitatory cells, called non-excitatory cells (NEC) such as cells of the ventricular and auricular walls. In order to understand cardiac calcium homeostasis, it is, therefore, important to study the calcium dynamics taking into account both types of cardiac cells. Here we have developed a model to capture the calcium dynamics in excitatory and non-excitatory cells taking into consideration the gap junction mediated calcium ion transfer from excitatory cell to non-excitatory cell. Our study revealed that the gap junctional coupling between excitatory and non-excitatory cells plays important role in the calcium dynamics. It is observed that any reduction in the functioning of gap junction may result in abnormal calcium oscillations in NEC, even when the calcium dynamics is normal in EC cell. Sensitivity of gap junction is observed to be independent of the pacing rate and hence a careful monitoring is required to maintain normal cardiomyocyte condition. It also highlights that sarcoplasmic reticulum may not be always able to control the amount of cytoplasmic calcium under the condition of calcium overload.
钙离子有助于心肌细胞动作电位的产生，并负责心脏的兴奋 - 收缩偶联。心肌具有特殊的细胞群，称为兴奋性细胞（EC），如能够自动产生动作电位的窦房结细胞，以及接收兴奋性细胞信号的细胞，称为非兴奋性细胞（NEC），如心室和心房壁的细胞。因此，为了理解心脏钙稳态，考虑到这两种类型的心脏细胞来研究钙动力学很重要。在这里，我们开发了一个模型，以考虑到间隙连接介导的钙离子从兴奋性细胞向非兴奋性细胞的转移，来捕捉兴奋性和非兴奋性细胞中的钙动力学。我们的研究表明，兴奋性和非兴奋性细胞之间的间隙连接偶联在钙动力学中起重要作用。据观察，即使EC细胞中的钙动力学正常，间隙连接功能的任何降低都可能导致NEC中异常的钙振荡。间隙连接的敏感性被观察到与起搏速率无关，因此需要仔细监测以维持正常的心肌细胞状态。它还强调，在钙超载的情况下，肌浆网可能并不总是能够控制细胞质钙的量。
