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

Heunks, Leo M. A., Mark J. Cody, Paige C. Geiger, P. N. Richard Dekhuijzen, and Gary C. Sieck. Nitric oxide impairs Ca21 activation and slows cross-bridge cycling kinetics in skeletal muscle. J Appl Physiol 91: 2233–2239, 2001.—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 Ca21 concentrations (pCa, negative logarithm of Ca21 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 forcegenerating state was estimated by the ratio of stiffness during maximal (pCa 4.0) and submaximal (pCa 5.6) Ca21 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) Ca21 activation. However, the effects of Sp-NO were more pronounced during submaximal Ca21 activation. Sp-NO also reduced the rate constant for force redevelopment but only during submaximal Ca21 activation. We conclude that Sp-NO reduces Ca21 sensitivity by decreasing the number of cross bridges in the strongly bound state and also impairs cross-bridge cycling kinetics during submaximal activation.