论文标题
一种自发抗心律失常的理论模型
A theoretic model for sonogenetic antiarrhythmia
论文作者
论文摘要
由于其非侵入性,高安全性和强渗透性的优势,因此可以用作心律不齐的新替代方法。在通过声遗传学治疗心律不齐时,心肌细胞被超声辐射力畸形。我们定量计算了在超声辐射力下心肌细胞的形状变化,而心肌细胞的变形导致膜张力的变化。膜张力由两个部分组成:细胞膜和细胞骨架之间的质膜张力和皮质张力。由于质膜张力主要在现有实验中考虑,因此我们提出了超声辐射力与质膜张力之间关系的定量模型。质膜张力与离子通道开口概率之间的玻尔兹曼关系是根据离子通道激活的实验结果提出的。最后,获得了超声辐射力的定量模型,以调节通过拉伸激活的离子通道的开口概率。基于此定量模型,我们提出了超声辐射力的调节机制,在超压力和超伸展下,并验证了这种机制可以消除声遗传学的心律失常。
Sonogenetics can be used as a new alternative for treating arrhythmia due to its advantages of noninvasive, high safety and strong penetration. In the treatment of arrhythmias by sonogenetics, cardiac myocytes are deformed by ultrasonic radiation force. We quantitatively calculated the shape variation of cardiomyocytes under ultrasonic radiation force, and the deformation of cardiomyocytes caused the change of membrane tension. Membrane tension consists of two parts, plasma membrane tension and cortical tension between the cell membrane and cytoskeleton. Since plasma membrane tension was mainly considered in existing experiments, we proposed a quantitative model of the relationship between ultrasonic radiation force and plasma membrane tension. The Boltzmann relationship between plasma membrane tension and ion channel opening probability is presented based on the experimental results of ion channel activation by stretching. Finally, a quantitative model was obtained for ultrasonic radiation force to regulate the opening probability of ion channel activated by stretching. Based on this quantitative model, we proposed the regulation mechanism of ultrasonic radiation force under hypercompression and hyperstretching, and verified that this mechanism can eliminate arrhythmias by sonogenetics.