The effect of diazepam on potassium contractures, contraction threshold, and resting tension in rat skeletal muscles

The effects of diazepam on potassium contractures, contraction threshold, and resting tension have been examined in rat soleus muscle fibres. Two actions of the drug were defined that could not be attributed to changes in the resting membrane potential or depolarization in high potassium solutions. The major effect was an increase in the amplitude of submaximal tension during either twitches or potassium contractures and an increase in resting tension. At 400 microM diazepam, there was (a) a fourfold increase in 40 mM potassium contracture tension, (b) a negative shift of 8 mV in the membrane potential for half maximum tension estimated from the best fit of a Boltzmann-type equation to average potassium contracture data, (c) a negative shift of 8 mV in the threshold for contraction measured under voltage clamp conditions, and (d) a contracture of variable amplitude to a level that was occasionally equivalent to maximum tetanic tension. These potentiating actions of diazepam depended on drug concentration within the range of 100-800 microM. In contrast, the second effect of diazepam, depression of maximum tension by 10-15%, was independent of drug concentration between 100 and 400 microM. The results support the idea that diazepam produces an increase in resting myoplasmic calcium concentrations.