Functional and structural differences between skinned and intact muscle preparations

Alex Lewalle; Kenneth S. Campbell; Stuart G. Campbell; Gregory N. Milburn; Steven A. Niederer

doi:10.1085/jgp.202112990

Functional and structural differences between skinned and intact muscle preparations

Alex Lewalle, Kenneth S. Campbell, Stuart G. Campbell, Gregory N. Milburn, Steven A. Niederer

Biomedical Engineering Department

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e202112990
Journal	The Journal of general physiology
Volume	154
Issue number	2
DOIs	https://doi.org/10.1085/jgp.202112990
Publication status	Published - 7 Feb 2022

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10.1085/jgp.202112990

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title = "Functional and structural differences between skinned and intact muscle preparations",

abstract = "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.",

author = "Alex Lewalle and Campbell, {Kenneth S.} and Campbell, {Stuart G.} and Milburn, {Gregory N.} and Niederer, {Steven A.}",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2022 Lewalle et al.",

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AU - Campbell, Kenneth S.

AU - Campbell, Stuart G.

AU - Milburn, Gregory N.

AU - Niederer, Steven A.

N1 - Funding 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. Publisher Copyright: © 2022 Lewalle et al.

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N2 - 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.

AB - 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.

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ER -

Functional and structural differences between skinned and intact muscle preparations

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