Acta Biologica 29. (1978)
2. szám - Kónya L.–Jóna I.–Kövér A.–Aradi F.: Determination of dose and time dependence of muscle contractures elicited by caffeine
Acta biol Acad. Sei. hung. 29 (2), 129 —137 (1978) DETERMINATION OF DOSE AND TIME DEPENDENCE OF MUSCLE CONTRACTURES ELICITED BY CAFFEINE L. KÓNYA, I. JÓNA, A. KÖVÉR, and F. ÁRADI CENTRAL RESEARCH LABORATORY, UNIVERSITY MEDICAL SCHOOL, DEBRECEN, AND CENTRAL LABORATORY, MEDICAL UNIVERSITY, PÉCS, HUNGARY (Received 1978-02 — 23) Abstract Caffeine contractures were registered on fibre bundle preparations of frog m. semitendinosus. The drug was applied to muscles in normal Ringer for 30 min in concentrations of 3 — 40 mM. Biphasic contractures were found in all cases above mechanical threshold concentration of caffeine (2.35 mM. calculated value). Parameter values belonging to the two contracture phases (amplitude, zllx 12; time, tx t2) were analysed by computer programmes in correlation with caffeine concentration. It was found that 1. both contracture phases have the same concentration threshold of caffeine; 2. a caffeine-binding site with Kj = 24.6 mM can be supposed in the surface membrane being responsible for the induction of the first contracture phase of caffeine in the muscle; 3. caffeine has a concentration-dependent action on the surface membrane binding site with a tendency of muscles to contract to zero length at infinite caffeine concentration; 4. the speed of caffeine action is practically equal to the solution exchange emphasizing the action site at the surface membrane of the muscle (sarcolemma and T-tubule membrane); 5. the second caffeine contracture phase develops with maximal amplitude above contracture threshold concentration, during which muscles contract to about 40% of their slack length; this corresponds to a sarcomere length less than that of the myosin filament, consequently, a shortening of this filament must also take place; 6. the concentration dependence of the second contracture phase results in a monotonie decrease of t2 with increasing caffeine concentration. A possibility for the mechanism of caffeine action through binding to proteins involved in the regulation of intracellular calcium level is discussed. Introduction The effect of caffeine on the mechanical response of skeletal muscle depends on the caffeine concentration, on the time for which caffeine is allowed to act, on the type of muscle preparation (single or multifibre), and also on the mode of registration (isometric or isotonic), etc. The threshold concentration of caffeine to elicit muscle contracture proved to be 2—3 mM in different experiments. Above this concentration, the caffeine action is graded, the measure of tension development or the size of contracture amplitude increases with increasing caffeine concentration [2]. Caffeine contractures of muscle show a time-dependence. On single fibre preparations, the tension or the contracture amplitude has irregular Ada Biologica Acaderniae Scientiarum Hungaricae 29, 1978