2 SITES OF ACTION FOR LCB29 (IDROCILAMIDE) IN DEPRESSING MECHANICAL TENSION OF RAT SOLEUS MUSCLE-FIBERS

The effects of 50 mu M LCB29 (idrocilamide) were tested on depolarizat ion-induced and caffeine contractures of rat soleus muscle fibers. Whe n applied intracellularly by free diffusion in cut-end voltage-clamped fibers, LCB29 decreased tension amplitude by about 25%. The same amou nt of inhibition by LCB29 was observed on contractures induced by 6 mM caffeine. The drug did not affect the repriming of caffeine contractu res, indicating that internal recycling of calcium was not affected. T he voltage-dependent inactivation of tension was facilitated by extern al application of LCB29. This effect was calcium dependent, so that th e greater the external calcium concentration, the greater the drug eff ectiveness. The spontaneous relaxation of Kf(+) 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.