Myosin and Troponin Peptides Affect Calcium Sensitivity of Skinned Muscle Fibres
It is well known that the force developed by the contractile system depends on the calcium ion concentration in the medium surrounding the myofilaments as well as on the Ca++-sensitivity or the calcium responsiveness of the contractile apparatus (Rüegg 1988). We have studied the effect of peptides derived from troponin-I and the 20kDa domain of myosin subfragment-1 which affect the calcium sensitivity of the contractile system. These effects are of particular interest in the case of cardiac muscle, where the relationship between intracellular calcium concentration and force may vary over a wide range. For instance, hearts that are subjected to long periods of ischemia may develop a contracture even at basal levels of free calcium (Allshire et al. 1987, Allen and Orchard 1987). This is probably due to a potentiation of ATPase and force generation occurring at low levels of ATP (Winegrad 1979). Indeed, Güth and Potter (1987) showed, that attached crossbridges increase the calcium responsiveness of skinned fibres at low ATP-concentrations, when some crossbridges are in the nucleotide-free state. Under these conditions, the contractile system is activated, and even potentiated at very low calcium ion concentrations which normally do not elicit a contraction (cf. Weber and Murray 1973). In vitro, such a potentiation also occurs in the presence of excess of myosin subfragment-1, S1, indicating that there is cooperativity in the binding of S-1 to actin (Greene and Eisenberg 1980). Here we propose as a working hypothesis that it may be the actin-binding region of subfragment-1 around the SH-1 group which by, interacting with actin, is capable of “turning on” actin, so that calcium responsiveness increases.
KeywordsCardiac Muscle Fibre Peptide Mimetics Calcium Responsiveness Skinned Fibre Contractile System
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- FABIATO A., FABIATO F. (1979): Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J. Physiol. (Paris) 75:463–505.Google Scholar
- KRAFT Th., TRAYER I.P., BRENNER B. (1991): Myosin peptides and cross-bridge kinetics. In Rüegg JC (ed): Peptides as probes in muscle research. Springer Verlag Heidelberg (this volume).Google Scholar
- MORITA F., KATOH T., SUZUKI R., ISONISHI K., HORIK, ETO M. (1991): An Actin-Binding Site on Myosin. In Rüegg JC (ed): Peptides as probes in muscle research. Springer Verlag — Heidelberg (this volume).Google Scholar
- RüEGG J.C. (1988): Calcium in Muscle Activation. Springer-Verlag. Berlin-Heidelberg-New York-London-Paris-Tokyo, 2nd printing.Google Scholar
- TRAYER I.P., KEANE A.M., MURAD Z., RüEGG J.C., SMITH K.J. (1991): The use of peptide mimetics to define the actin-binding sites on the head of the myosin molecule In: Rüegg JC (ed): Peptides as probes in muscle research. Springer Verlag — Heidelberg (this volume).Google Scholar
- VAN EYK J., SöNNICHSEN F.D., SYKES B.D., HODGES R.S. (1991): Interaction of actin 1–28 with myosin and troponin-I and the importance of these interactions to muscle regulation In: Rüegg JC (ed): Peptides as probes in muscle research. Springer Verlag — Heidelberg (this volume).Google Scholar
- WINEGRAD S. (1979): Electromechanical coupling in heart muscle. In: Berne RM, Sperelakis N, Geiger SR (eds) The cardiovascular system. Am. Physiol. Soc. Bethesda, pp 393–428 (Handbook of phisiology, sect 2, vol I).Google Scholar