Figure 1.

Probenecid and carbenoxolone depress voltage-activated SR Ca²⁺ release. (A) Representative examples of rhod-2 fluorescence transients (F/F₀ traces) and corresponding calculated SR Ca²⁺ release flux (dCa_Tot/dt) elicited by the voltage-clamp pulse protocol shown on top, in a control fiber, in a fiber equilibrated in the presence of probenecid, and in a fiber equilibrated in the presence of carbenoxolone. (B) Voltage-dependence of the peak amplitude of SR Ca²⁺ release (left) and of the corresponding total amount of released Ca²⁺ (right) in the control group of fibers (black) and in the groups of fibers treated with probenecid (red) and carbenoxolone (blue), all tested as shown in A. Individual datapoints from each muscle fiber are shown, with the corresponding Boltzmann fit superimposed (continuous line). An identical symbol is used for fibers from the same mouse. The control, probenecid, and carbenoxolone datasets are from 11 fibers from six mice, 10 fibers from four mice, and 8 fibers from three mice, respectively. Data from muscle fibers issued from the same mouse are shown with the same symbol. The inset in each panel shows the corresponding mean (±SD) values in each group with the x and y scale covering the same ranges as in the main panel. (C) Individual and mean (±SD) values for the Boltzmann parameters in the three groups of muscle fibers. Statistical difference between the parameters in the control and either the probenecid or the carbenoxolone groups was assessed using the nested analysis described by Eisner (2021).