Journal of Applied Physiology Journal of Applied Physiology
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J Appl Physiol 91: 2233-2239, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 5, 2233-2239, November 2001

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

Leo M. A. Heunks1, Mark J. Cody2, Paige C. Geiger2, P. N. Richard Dekhuijzen1, and Gary C. Sieck2

1 Department of Pulmonary Diseases, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands; and 2 Departments of Anesthesiology and Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55902

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.

rabbit psoas; spermine NONOate; rate of force redevelopment; stiffness


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