X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin
MetadataShow full item record
AbstractThe stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15950
- Modeling Local X-ROS and Calcium Signaling in the Heart.
- Authors: Limbu S, Hoang-Trong TM, Prosser BL, Lederer WJ, Jafri MS
- Issue date: 2015 Nov 17
- Hypertrophic cardiomyopathy mutations increase myofilament Ca<sup>2+</sup> buffering, alter intracellular Ca<sup>2+</sup> handling, and stimulate Ca<sup>2+</sup>-dependent signaling.
- Authors: Robinson P, Liu X, Sparrow A, Patel S, Zhang YH, Casadei B, Watkins H, Redwood C
- Issue date: 2018 Jul 6
- High-mobility group box 1 (HMGB1) impaired cardiac excitation-contraction coupling by enhancing the sarcoplasmic reticulum (SR) Ca(2+) leak through TLR4-ROS signaling in cardiomyocytes.
- Authors: Zhang C, Mo M, Ding W, Liu W, Yan D, Deng J, Luo X, Liu J
- Issue date: 2014 Sep
- Balanced changes in Ca buffering by SERCA and troponin contribute to Ca handling during β-adrenergic stimulation in cardiac myocytes.
- Authors: Briston SJ, Dibb KM, Solaro RJ, Eisner DA, Trafford AW
- Issue date: 2014 Nov 1
- X-ROS signaling in the heart and skeletal muscle: stretch-dependent local ROS regulates [Ca²⁺]i.
- Authors: Prosser BL, Khairallah RJ, Ziman AP, Ward CW, Lederer WJ
- Issue date: 2013 May