Negative inotropic effect of heparin on tension development in rat skinned skeletal muscle fibres

Heparin inhibits inositol trisphosphate receptors, particularly in smooth muscle, but its effect on skeletal muscle is controversial. Our study showed that heparin induced a decrease in the amplitude of 10 mM caffeine-induced contracture in slow and fast saponin-skinned fibres. Moreover, measurements on Triton X-100-skinned fibres in soleus muscle showed that heparin alone decreased maximal Ca2(+)-activated tension and Ca2+ sensitivity of contractile proteins, whereas no significant effect was observed in extensor digitorum longus muscle. However, in the presence of caffeine, heparin decreased maximal Ca2(+)-activated tension in both muscles. It would appear that the heparin-induced decrease in the amplitude of caffeine contracture in rat skeletal muscle was not related to a direct inhibition of Ca2+ release from sarcoplasmic reticulum but to a desensitising effect of heparin and caffeine on myofilaments.