Figure 2.

Effect of probenecid at 0.5 and at 2 mM on 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 0.5 mM probenecid, and a fiber equilibrated in the presence of 2 mM probenecid. (B) Voltage-dependence of the peak amplitude of SR Ca²⁺ release (dCa_Tot/dt, top panels) and of the corresponding total amount of released Ca²⁺ (Ca_Tot, bottom panels) in the control group of fibers (black) and the groups of fibers treated with probenecid (red and green), all tested as shown in A. Individual datapoints from each muscle fiber are shown, with the corresponding Boltzmann fit superimposed (continuous line). The control, probenecid 0.5 mM, and probenecid 2 mM datasets are from 13 fibers from five mice, 10 fibers from three mice, and 9 fibers from three mice, respectively. Data from muscle fibers issued from the same mouse are shown with the same symbol. The inset on the right in each panel shows 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 a nested analysis (Eisner, 2021).