Methylxanthines, as caffeine and theophylline, are frequently ingested by humans, used as therapeutic agents and used as experimental tools. The contraction of mammalian skeletal muscle was thought to be relatively insensitive to low doses of methylxanthines, particularly caffeine and theophylline, but alterations in muscle contraction properties have been routinely observed with caffeine and theophylline doses equivalent to those found in humans ingesting coffee and on therapeutic regimens. Thus an aim of this work is, with the assistance of students, to investigate the action of both high and low theophylline levels on muscle contraction and energy balance in metabolicly-stable mammalian muscle models. For this purpose isolated soleus and EDL muscles of the rat will be used. Theophylline-evoked twitch potentiation and contracture dose response curves will be ascertained for both isolated preparations. In addition, theophylline's effect on high energy phosphate levels in these muscles will be compared to effects obtained in frog skeletal muscle. The results with theophylline will then be compared with results previously obtained with caffeine to determine if any differences exist in the action of these two methylxanthines on muscle contraction. A clearer picture of direct muscle actions of theophylline should emerge, including if theophylline, like caffeine, can exert a direct effect on limb muscle contraction at therapeutic levels. Also, by using calcium agonists/antagonists to modify theophylline's action, a better understanding of the mechanism of theophylline's action in skeletal muscle should emerge. Students assistants will be able to participate in all aspects. They will gain experience in both standard physiological as well as biochemical techniques and via other supportive activities be encouraged to pursue biomedical research careers.
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