APPS November 2002 Meeting Abstract 2419

In recent years the roles of reactive oxygen species (ROS) in biological systems have been of interest due to their paradoxical ability to act both as toxic agents and as physiological signalling molecules. It has been suggested that ROS, such as hydrogen peroxide (H₂O₂), can modulate smooth muscle contractility. Rather surprisingly it has been reported that H₂O₂ can induce both contraction and relaxation of vascular smooth muscle, as well as modify contractile responses to stimulants^1,2. There is, however, uncertainty as to the role of Ca²⁺ in mediating responses to H₂O₂. This study employed simultaneous recordings of force and intracellular Ca²⁺ concentration ([Ca²⁺]_i) to investigate the effects of H₂O₂ on contractile function of the rat anococcygeus muscle and relate these effects to intracellular Ca²⁺ movements. H₂O₂ alone produced a concentration dependent (0.1 to 1.0 mM) increase in [Ca²⁺]_i, that was dependent on extracellular Ca²⁺ and occurred without a comparable increase in force. At 0.5mM H₂O₂, [Ca²⁺]_i rose to 140 ą 31% of the level reached during high K⁺ stimulation while force rose to only 6 ą 2% of the high K⁺ force. When H₂O₂ was added to muscles pre-contracted with high K⁺ or phenylephrine it had no detectable immediate effect on force, however, it further increased [Ca²⁺]_i. Following prior exposure to H₂O₂ the contractile response to high K⁺and phenylephrine was reduced (by approximately 15% and 25% respectively, at 0.5 mM H₂O₂), however, the magnitude of the increase in [Ca²⁺]_iwas greater. The results demonstrate that H₂O₂ increases [Ca²⁺]_i in rat anococcygeus muscle and induces an apparent dissociation between [Ca²⁺]_i and force. The specific pathway through which Ca²⁺ enters the cells in the presence of H₂O₂ remains to be identified as do the mechanisms responsible for the observed dissociation between [Ca²⁺]_i and force in the presence of H₂O₂.