The inhibitory effect of α-methyl-5-HT on ATP-activated currents in rat dorsal root ganglion neurons

Abstract The purpose of this study was to explore the inhibitory effect of α-methyl-5- hydroxytryptamine (α-methyl-5-HT) on ATP-activated current (IATP) in rat dorsal root ganglion (DRG) neurons. Whole-cell patch clamp experiment was performed on cultured rat DRG neurons. One minute after treatment with α-methyl-5-HT, ATP (10-4 mol/L) activation current in rat DRG neurons was inhibited. However, this inhibitory effect was independent of the current caused by α-methyl-5-HT. The dose-response curve for IATP showed that α-methyl-5-HT significantly shifted it. The Kd values of ATP-activated currents before and after the pre-addition of α-methyl-5-HT were similar (4.23×10-5 mol/L vs. 6.81×10-5 mol/L). Furthermore, cyproheptadine (10-6 mol/L), an antagonist of 5-HT2 receptor, can reverse the inhibition of α-methyl-5-HT. After intracellular dialysis of KN93 (CaMKII inhibitor) and H7 (PKC inhibitor), this inhibition was also completely eliminated. In conclusion, our results showed that α-methyl-5-HT inhibited ATP-activated current through activating the 5-HT2 receptor and resulting in phosphorylation of the ATP receptor. It was caused by the activation of G protein coupled receptor and corresponding intracellular signaling transduction cascade.