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.
Andrade
F H
FH
Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Reid
M B
MB
Allen
D G
DG
Westerblad
H
H
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D012977:Sodium Nitrite / Q000494:pharmacology
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; C024940:S-nitroso-N-acetylcysteine; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D012977:Sodium Nitrite; D002118:Calcium; D000111:Acetylcysteine