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The effects of 50 microM LCB29 (idrocilamide) were tested on depolarization-induced and caffeine contractures of rat soleus muscle fibers. When applied intracellularly by free diffusion in cut-end voltage-clamped fibers, LCB29 decreased tension amplitude by about 25%. The same amount of inhibition by LCB29 was observed on contractures induced by 6 mM caffeine. The drug did not affect the repriming of caffeine contractures, indicating that internal recycling of calcium was not affected. The voltage-dependent inactivation of tension was facilitated by external application of LCB29. This effect was calcium dependent, so that the greater the external calcium concentration, the greater the drug effectiveness. The spontaneous relaxation of K+ contractures was also accelerated by LCB29. It is concluded that LCB29 acts intracellularly by decreasing sarcoplasmic reticulum calcium release and externally by facilitating the voltage-dependent inactivation of the voltage sensor for excitation-contraction coupling.

The effect of LCB29 was tested on twitch characteristics, tetanic tension, and K+ and voltage-clamp contractures of rat soleus muscle fibers. In concentrations ranging from 10(-6) to 5 x 10(-4) M, LCB29 simultaneously inhibited the twitch amplitude, the maximum rate of tension development, and the maximum rate of relaxation. In concentrations ranging from 10(-5) to 10(-4) M, tetanic tension (100 Hz, 1 s) was inhibited by the same amount. The effect of 5 x 10(-5) M LCB29 was studied on K+ contractures and contractures induced, under voltage-clamp conditions, by long-lasting depolarizations. Its effect was significantly stronger than those on twitch and tetanic tension. In addition, LCB29 had a dual effect on strength--duration curves for mechanical threshold. It increased both the rheobasic potential and the steepness of the curve. It is concluded that LCB29 exerts a direct myorelaxant effect on rat soleus muscle; two sites of action are probably involved.