APPS November 2002 Meeting Abstract 2419


EFFECT OF HYDROGEN PEROXIDE ON INTRACELLULAR CALCIUM AND FORCE IN RAT ANOCOCCYGEUS MUSCLE

Ruchi Patel, Igor R. Wendt, Department of Physiology, Monash University, Vic. 3800.

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 stimulants1,2. 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 31% of the level reached during high K+ stimulation while force rose to only 6 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+]i was 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.

(1) Barlow RS, El-Mowafy AM, White RE. American Journal of Physiology. 2000;279:H475-H483.

(2) Jin N, Rhoades RA. American Journal of Physiology. 1997;272:H2686-H2692.


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