Figure 7. Block of plateau potentials by ranolazine in 9-AC treated muscle is associated with lessening of depolarization during repetitive firing.

(A) Examples of the response to a 200 ms injection of depolarizing current at baseline and following treatment with 40 µM ranolazine. (B) Examples of the response to 2 s of stimulation at 20 Hz. The vertical arrow points to the 30th action potential in each trace, which was used for the analysis of differences between ranolazine untreated and ranolazine treated muscle (D–F). (C) Plots of the membrane potential during the 8 ms encompassing the action potential and the 42 ms encompassing the interspike interval for the untreated and ranolazine traces shown in B. Each point represents the value for a single action potential during the 2 s of 20 Hz stimulation. Action potential MP = the mean membrane potential during the 8 ms encompassing the action potential, Inter-AP MP = the mean membrane potential during the 42 ms interspike interval. (D) Plot of the mean membrane potential during the last 500 ms of stimulation. Each point represents an animal average derived from at least four fibers without (n = 5) and with treatment with ranolazine (n = 5). The horizontal line represents the mean. (E and F) Plots of the mean membrane potential during the 30th action potential and the 30th interspike interval. * indicates p=0.005 (t-test), **p=0.01 (t-test).