Effect of nitric oxide on single skeletal muscle fibres from the mouse

1. Single skeletal muscle fibres from a mouse foot muscle were used to investigate the effects of nitric oxide on contractile function. 2. We measured force production and myoplasmic free Ca²⁺ concentration ([Ca²⁺](i)) in single fibres exposed to the nitric oxide donors S-nitroso-N-acetylcysteine (SNAC) and nitroprusside. 3. The nitric oxide donors reduced myofibrillar Ca²⁺ sensitivity, whereas [Ca²⁺](i) transients were increased during submaximal tetani. Force was largely unchanged. SNAC did not, change maximum shortening velocity, the rate of force redevelopment, or force production at saturating [Ca²⁺](i). 4. The guanylyl cyclase inhibitor LY83583 increased tetanic [Ca²⁺](i) but had no effect on Ca²⁺ sensitivity. LY83583 did not prevent the decrease in myofibrillar Ca²⁺ sensitivity in response to SNAC. The oxidizer sodium nitrite increased tetanic [Ca²⁺](i) and decreased myofibrillar Ca²⁺ sensitivity. 5. We conclude that under our experimental conditions nitric oxide impairs Ca²⁺ activation of the actin filaments which results in decreased myofibrillar Ca²⁺ sensitivity.