Institute of Immunology and Physiology, Russian Academy of Sciences, Pervomajskaya Str. 106, 620049 Yekaterinburg, Russia.
Department of Therapy, Ural State Medical University, Repina Str. 3, 620028 Yekaterinburg, Russia.
Cells. 2022 Nov 28;11(23):3809. doi: 10.3390/cells11233809.
Acetylcholine (ACh) is the neurotransmitter of the parasympathetic nervous system that modulates cardiac function, and its high concentrations may induce atrial fibrillation. We compared the ACh action on the mechanical function of single cardiomyocytes from the left atria (LA) and the right atria (RA). We exposed single rat LA and RA cardiomyocytes to 1, 10, and 100 µM ACh for 10-15 min and measured the parameters of sarcomere shortening-relengthening and cytosolic calcium ([Ca]) transients during cell contractions. We also studied the effects of ACh on cardiac myosin function using an in vitro motility assay and analyzed the phosphorylation level of sarcomeric proteins. In LA cardiomyocytes, ACh decreased the time to peak sarcomere shortening, time to 50% relengthening, and time to peak [Ca] transients. In RA cardiomyocytes, ACh affected the time of shortening and relengthening only at 10 µM. In the in vitro motility assay, ACh reduced to a greater extent the sliding velocity of F-actin over myosin from LA cardiomyocytes, which was accompanied by a more pronounced decrease in phosphorylation of the myosin regulatory light chain (RLC) in LA cardiomyocytes than in RA cardiomyocytes. Our findings indicate that ACh plays an important role in modulating the contractile function of LA and RA, provoking more pronounced changes in the time course of sarcomere shortening-relengthening and the kinetics of actin-myosin interaction in LA cardiomyocytes.
乙酰胆碱（ACh）是副交感神经系统的神经递质，调节心脏功能，其高浓度可能会引发心房颤动。我们比较了 ACh 对左心房（LA）和右心房（RA）单个心肌细胞机械功能的作用。我们将单个大鼠 LA 和 RA 心肌细胞暴露于 1、10 和 100µM ACh 中 10-15 分钟，并在细胞收缩期间测量肌节缩短-延长和细胞质钙（[Ca]）瞬变的参数。我们还使用体外运动分析研究了 ACh 对心肌肌球蛋白功能的影响，并分析了肌节蛋白的磷酸化水平。在 LA 心肌细胞中，ACh 缩短了肌节缩短的峰值时间、50%再延长时间和峰值 [Ca] 瞬变时间。在 RA 心肌细胞中，ACh 仅在 10µM 时影响缩短和再延长的时间。在体外运动分析中，ACh 更大程度地降低了来自 LA 心肌细胞的肌球蛋白上 F-肌动蛋白的滑动速度，这伴随着 LA 心肌细胞中肌球蛋白调节轻链（RLC）的磷酸化程度比 RA 心肌细胞更明显降低。我们的发现表明，ACh 在调节 LA 和 RA 的收缩功能中发挥重要作用，在 LA 心肌细胞中引起更明显的肌节缩短-延长时间过程和肌动球蛋白相互作用的动力学变化。
