Inhibition of NCX Reverse Mode Activity

We used SN-6 (2-[[4-[(4-Nitrophenyl)methoxy]phenyl]methyl]-4-thiazolidine carboxylic acid ethyl ester) and KB-R7943 (2-[2-[4-(4-Nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate) potent inhibitors of the NCX reverse mode activity for NCX1 and NCX3, respectively, which were purchased from R&D System (Minneapolis, MN, USA). SN-6 and KB-R7943 were dissolved in dimethyl sulfonic acid (0.1%) and phosphate-buffered saline (pH 7.4) using sonication (80 kHz, 100% power). The solutions containing either SN-6 (0, 3, 10 mg/kg, p.o.) or KB-R7943 (0, 3, 10 mg/kg, p.o.) were freshly prepared before their administration, as previously described [29 (link),30 (link)]. After four weeks of training, animals were randomly assigned into eight groups (n= 12) including female KB-R7943-3 (KB-R7943, 3 mg/kg), female KB-R7943-10 (KB-R7943, 10 mg/kg), male KB-R7943-3 (KB-R7943, 3 mg/kg), male KB-R7943-10 (KB-R7943, 10 mg/kg), female SN-6-3 (KB-R7943, 3 mg/kg), female SN-6-10 (SN-6, 10 mg/kg), male SN-6-3 (SN-6, 3 mg/kg), and male SN-6-10 (SN-6, 10 mg/kg). On Mondays, animals received the vehicle; on Wednesdays, animals received the tested drug, either SN-6 or KB-R7943; and on Fridays, they were examined to see the long-lasting effects of the drugs.