4.3 Review

Functional and structural differences between skinned and intact muscle preparations

Journal

JOURNAL OF GENERAL PHYSIOLOGY
Volume 154, Issue 2, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.202112990

Keywords

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Categories

Funding

  1. UK Engineering and Physical Sciences Research Council [EP/M012492/1, NS/A000049/1, EP/P01268X/1]
  2. British Heart Foundation [PG/15/91/31812, PG/13/37/30280, SP/18/6/33805, PG/21/10534]
  3. National Institutes of Health [NIH R01-HL152256, NIH TR001998, ERC PREDICT-HF 864055, WT 203148/Z/16/Z]
  4. European Research Council [NIH HL133359]
  5. Wellcome Trust
  6. Kings Health Partners London National Institute for Health Research (NIHR) Biomedical Research Centre [NIH HL146676]
  7. National Science Foundation
  8. [1653160]

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Myofilaments and associated proteins form sarcomeres, which are responsible for muscle contraction. Skinned muscle preparations have been instrumental in understanding the contractile mechanisms of skeletal and cardiac muscle. However, there are inherent differences between skinned and intact muscle that pose challenges for experimentalists.
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. Lewalle et al. review differences in skinned and intact muscle preparations.

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