Myofilaments and their associated proteins, which together constitute the sarcomeres, provide the molecular-level basis for contractile function in all muscle types. In intact muscle, sarcomere-level contraction is strongly coupled to other cellular subsystems, in particular the sarcolemmal membrane. Skinned muscle preparations (where the sarcolemma has been removed or permeabilized) are an experimental system designed to probe contractile mechanisms independently of the sarcolemma. Over the last few decades, experiments performed using permeabilized preparations have been invaluable for clarifying the understanding of contractile mechanisms in both skeletal and cardiac muscle. Today, the technique is increasingly harnessed for preclinical and/or pharmacological studies that seek to understand how interventions will impact intact muscle contraction. In this context, intrinsic functional and structural differences between skinned and intact muscle pose a major interpretational challenge. This review first surveys measurements that highlight these differences in terms of the sarcomere structure, passive and active tension generation, and calcium dependence. We then highlight the main practical challenges and caveats faced by experimentalists seeking to emulate the physiological conditions of intact muscle. Gaining an awareness of these complexities is essential for putting experiments in due perspective.
|Journal||Journal of General Physiology|
|State||Published - Feb 7 2022|
Bibliographical noteFunding Information:
S.A. Niederer acknowledges support from the UK Engineering and Physical Sciences Research Council (grant nos. EP/ M012492/1, NS/A000049/1, and EP/P01268X/1), the British Heart Foundation (grant nos. PG/15/91/31812, PG/13/37/30280, SP/18/6/ 33805, and PG/21/10534), the National Institutes of Health (grant no. NIH R01-HL152256), European Research Council (grant no. ERC PREDICT-HF 864055), Wellcome Trust (grant no. WT 203148/Z/16/ Z), and Kings Health Partners London National Institute for Health Research (NIHR) Biomedical Research Centre. S.G. Campbell acknowledges support from the National Science Foundation CAREER award 1653160. K.S. Campbell acknowledges support from the National Institutes of Health (grants nos. NIH HL133359, NIH HL146676, and NIH TR001998). The authors declare no competing financial interests.
© 2022 Lewalle et al.
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