Nitric oxide impairs Ca2+ activation and slows cross-bridge cycling kinetics in skeletal muscle

Leo M.A. Heunks, Mark J. Cody, Paige C. Geiger, P. N.Richard Dekhuijzen, Gary C. Sieck

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The effects of the nitric oxide (NO) donor spermine NONOate (Sp-NO, 1.0 mM) on cross-bridge recruitment and cross-bridge cycling kinetics were studied in permeabilized rabbit psoas muscle fibers. Fibers were activated at various Ca2+ concentrations (pCa, negative logarithm of Ca2+ concentration), and the pCa at which force was maximal (pCa 4.0) and ∼50% of maximal (pCa50 5.6) were determined. Fiber stiffness was determined using 1-kHz sinusoidal length perturbations, and the fraction of cross bridges in the force-generating state was estimated by the ratio of stiffness during maximal (pCa 4.0) and submaximal (pCa 5.6) Ca2+ activation to stiffness during rigor (at pCa 4.0). Cross-bridge cycling kinetics were evaluated by measuring the rate constant for force redevelopment after quick release (by 15% of optimal fiber length, Lo) and restretch of the fiber to Lo. Exposing fibers to Sp-NO for 10 min reduced force and the fraction of cross bridges in the force-generating state at maximal and submaximal (pCa50) Ca2+ activation. However, the effects of Sp-NO were more pronounced during submaximal Ca2+ activation. Sp-NO also reduced the rate constant for force redevelopment but only during submaximal Ca2+ activation. We conclude that Sp-NO reduces Ca2+ sensitivity by decreasing the number of cross bridges in the strongly bound state and also impairs cross-bridge cycling kinetics during submaximal activation.

Original languageEnglish (US)
Pages (from-to)2233-2239
Number of pages7
JournalJournal of applied physiology
Volume91
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Rabbit psoas
  • Rate of force redevelopment
  • Spermine NONOate
  • Stiffness

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Heunks, L. M. A., Cody, M. J., Geiger, P. C., Dekhuijzen, P. N. R., & Sieck, G. C. (2001). Nitric oxide impairs Ca2+ activation and slows cross-bridge cycling kinetics in skeletal muscle. Journal of applied physiology, 91(5), 2233-2239. https://doi.org/10.1152/jappl.2001.91.5.2233