Bell Kaylyn M, Brown Alon T, Van Houten Sarah K, Blice-Baum Anna C, Kronert William A, Loya Amy K, Camillo Jared Rafael T, Cammarato Anthony, Corr David T, Bernstein Sanford I, Swank Douglas M
Department of Biological Sciences & Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York.
Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York.
Biophys J. 2025 Feb 18;124(4):651-666. doi: 10.1016/j.bpj.2025.01.001. Epub 2025 Jan 10.
Stretch activation (SA), a delayed increase in force production after rapid muscle lengthening, is critical to the function of vertebrate cardiac muscle and insect asynchronous indirect flight muscle. SA enables or increases power generation in muscle types used in a cyclical manner. Recently, myosin isoform expression has been implicated as a mechanism for varying the amplitude of SA in some muscle types. For instance, we found that expressing a larval Drosophila myosin isoform in a muscle type with minimal SA, the Drosophila jump muscle, substantially increased SA amplitude and enabled positive cyclical power generation. To test whether other myosin isoforms could increase SA amplitude and whether the Drosophila heart benefits from SA, we identified two Drosophila cardiac myosin isoforms, CardM1 and CardM2, and expressed them in Drosophila jump muscle. CardM1, CardM2, and control jump muscle fibers all displayed the characteristic phase 3 of SA, with CardM2 SA amplitude ∼60% greater than that of CardM1 and control fibers. Increasing [P] from 0 to 16 mM increased CardM2 SA tension amplitude by 74%, yet had minimal or no effect on CardM1 or control muscle SA amplitude. CardM2 displayed the most prominent phase 3 dip when we induced shortening deactivation, a delayed decrease in force after muscle shortening. The magnitude of CardM2 shortening deactivation tension was ∼50% greater than control or CardM1 fibers. This, along with its greater stretch-activated tension, caused CardM2 to be the only isoform to produce positive power when its fiber length was sinusoidally oscillated. The results support our hypotheses that some myosin isoforms enable greater SA tension levels and suggest that the Drosophila heart is benefiting from SA and shortening deactivation in a manner similar to vertebrate hearts.
拉伸激活（SA），即快速肌肉拉长后力量产生的延迟增加，对于脊椎动物心肌和昆虫异步间接飞行肌的功能至关重要。SA能够实现或增加以周期性方式使用的肌肉类型中的能量产生。最近，肌球蛋白同工型表达被认为是在某些肌肉类型中改变SA幅度的一种机制。例如，我们发现在SA最小的肌肉类型——果蝇跳跃肌中表达幼虫果蝇肌球蛋白同工型，会大幅增加SA幅度并实现正向周期性能量产生。为了测试其他肌球蛋白同工型是否能增加SA幅度以及果蝇心脏是否从SA中受益，我们鉴定了两种果蝇心脏肌球蛋白同工型CardM1和CardM2，并在果蝇跳跃肌中表达它们。CardM1、CardM2和对照跳跃肌纤维均显示出SA的特征性第3阶段，CardM2的SA幅度比CardM1和对照纤维大60%左右。将[P]从0增加到16 mM会使CardM2的SA张力幅度增加74%，但对CardM1或对照肌肉的SA幅度影响极小或无影响。当我们诱导缩短失活（肌肉缩短后力量的延迟降低）时，CardM2表现出最显著的第3阶段下降。CardM2缩短失活张力的幅度比对照或CardM1纤维大50%左右。这一点，连同其更大的拉伸激活张力，使得CardM2成为其纤维长度进行正弦振荡时唯一能产生正向能量的同工型。这些结果支持了我们的假设，即一些肌球蛋白同工型能够实现更高的SA张力水平，并表明果蝇心脏正以类似于脊椎动物心脏的方式从SA和缩短失活中受益。
