Blebbistatin

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Blebbistatin

Description

Blebbistatin is a widely used muscle and non-muscle myosin II-specific inhibitor that block contractile activity. Blebbistatin shows selectivity and high affinity for multiple class II myosins. Blebbistatin is commonly employed in respirometric experiments with permeabilized muscle fibers (pfi). Permeabilized muscle fibers are sensitive to low oxygen supply due to diffusion restrictions that limit mitochondrial respiration at the core of the fiber bundle. Therefore, hyperoxic conditions are required to counteract this limitation. Further studies have shown that the addition of blebbistatin in the respiration medium prevents fiber contraction, reduces the oxygen sensitivity and allows the study of ADP kinetics in pfi at normoxic oxygen levels. However, other studies described that the presence of blebbistatin does not prevent the oxygen dependence in pfi. Moreover, several limitations of blebbistatin i.e. low solubility in water, cytotoxicity and phototoxicity have been described.

Abbreviation: Bleb

Reference: Perry 2011 Biochem J


References: Blebbistatin

 YearReferenceOrganismTissue;cell
Doerrier 2019 MitoFit Preprint Arch EA2019Doerrier C, Gama-Perez P, Distefano G, Pesta D, Soendergaard SD, Chroeis KM, Gonzalez-Franquesa A, Goodpaster BH, Coen P, Larsen S, Gnaiger E, Garcia-Roves PM (2019) Inter-laboratory harmonization of respiratory protocols in permeabilized human muscle fibers. MitoFit Preprint Arch doi:10.26124/mitofit:ea19.MiPSchool.0009.HumanSkeletal muscle
Perry 2011 Biochem J2011Perry CG, Kane DA, Lin CT, Kozy R, Cathey BL, Lark DS, Kane CL, Brophy PM, Gavin TP, Anderson EJ, Neufer PD (2011) Inhibiting myosin-ATPase reveals a dynamic range of mitochondrial respiratory control in skeletal muscle. Biochem J 437:215-22.Human
Rat
Skeletal muscle
 YearReferenceOrganismTissue;cell
Doerrier 2019 MiP20192019
Carolina Doerrier
Inter-laboratory harmonization of respiratory protocols in permeabilized human muscle fibers.
HumanSkeletal muscle
Doerrier 2018 MiP2018a2018
Carolina Anneliese Doerrier
Inter-laboratory harmonization of protocols for mitochondrial function evaluation in permeabilized muscle fibers.
MouseSkeletal muscle
Bezuidenhout 2016a Abstract MitoFit Science Camp 20162016Comparison of oxygen dependence of respiration in permeabilized mouse skeletal muscle fibers in two respiration media, MiR06Cr and Buffer Z containing Ctl, Cr and Blebbistatin.MouseSkeletal muscle
  1. Kovács M, Tóth J, Hetényi C, Málnási-Csizmadia A, Sellers JR (2004) Mechanism of blebbistatin inhibition of myosin II. J Biol Chem 279(34):35557-63. - https://www.ncbi.nlm.nih.gov/pubmed/15205456
  2. Scandurra FM, Gnaiger E (2010) Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics. Adv Exp Med Biol 662:7-25 - Scandurra 2010 Adv Exp Med Biol
  3. Várkuti BH, Képiró M, Horváth IÁ, Végner L, Ráti S, Zsigmond Á, Hegyi G, Lenkei Z, Varga M, Málnási-Csizmadia A (2016) A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative. Sci Rep 6:26141 - https://www.ncbi.nlm.nih.gov/pubmed/27241904

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MitoPedia topics: Inhibitor