Effect of probenecid on whole muscle resting and tetanic tension. (A) Representative records of the tension response of an isolated EDL muscle to a 60-Hz train of field stimulation applied every 15 min. Following the first train, the extracellular Ringer solution was replaced by the same solution containing either only DMSO (top) or probenecid (bottom). (B) Resting tension from five isolated EDL muscles electrically stimulated as in Fig. 10 A, and challenged either with the control protocol (black) or with probenecid (red). In both groups, the first measurement was taken in the presence of the control Ringer solution. The right-most graph shows the mean (±SD) values from the two groups. (C) Corresponding results for the peak amplitude of the tetanic tension. Note that in these whole muscle experiments, the course of probenecid equilibration within the entire section of the muscle is likely to take much longer than in the single muscle fibers experiments. In addition, contraction of the muscle may favor intramuscle equilibration of the drug and promote its effect, making it look like a use-dependent effect.