Figure 7. Adenosine-induced depression of seizure activity is mediated by activation of A₁ ARs and requires the functions of Gα_i proteins and PKA.

A, Seizure events induced by bath application of picrotoxin at the saturated concentration (100 µM) in a rat slice at different times. An extracellular electrode containing ACSF was placed in layer III of the EC to record the seizure events. B, Time course of picrotoxin-induced seizure events (n = 7 slices). C, Seizure events recorded before, during and after the application of adenosine (100 µM). D, Summarized time course of adenosine-induced inhibition of seizure activity (n = 10 slices, p<0.001 vs. baseline, paired t-test). E, Concentration-response curve of adenosine-induced depression of seizure activity. Numbers in the parenthesis are the number of slices recorded from. F, Prior bath application of the A₁ AR inhibitor, DPCPX, blocked adenosine-induced depression of seizure events (n = 12 slices, p = 0.89 vs. baseline, paired t-test). G, Bath application of the A₁ AR agonist, NCPA, irreversibly suppressed the seizure events (n = 6 slices, p<0.001 vs. baseline, paired t-test). H, Application of antagonists to other ARs except A₁ ARs did not block adenosine-induced depression of epileptiform activity (One-way ANOVA followed by Dunnett test, *** p<0.001 vs. adenosine alone). I, Bath application of adenosine failed to depress significantly picrotoxin-induced seizure events in slices pretreated with PTX (n = 8 slices, p = 0.45 vs. baseline, paired t-test). J, Pretreatment of slices with and continuous bath application of the membrane permeable PKA inhibitor, KT5720, blocked adenosine-induced depression of seizure events (n = 8 slices, p = 0.7 vs. baseline, paired t-test).