On the voltage-dependent Ca2+ block of serotonin 5-HT3 receptors: a critical role of intracellular phosphates.

摘要: Natively expressed serotonin 5-HT(3) receptors typically possess a negative-slope conductance region in their I-V curve, due to voltage-dependent block by external Ca(2+) ions. However, almost all studies performed with heterologously receptors, this feature was not observed. Here we show that mere addition of ATP the pipette solution is sufficient reliably observe homomeric (h5-HT(3A)) and heteromeric (h5-HT(3AB)) HEK293 cells. A similar observed plethora molecules containing phosphate moiety, thus excluding role phosphorylation. substitution three arginines intracellular vestibule 5-HT(3A) counterpart residues from 5-HT(3B) subunit (RRR-QDA) previously shown dramatically increase single channel conductance. We find mutant have linear curve unaffected presence ATP, fractional current (Pf%) reduced (1.8 +/- 0.2%) compared receptor (4.1 0.2%), form (2.0 0.3%). Moreover, whereas decreased Pf% receptor, RRR-QDA mutant. Finally, found be critical for also hippocampal interneurons natively express receptors. Taken together, our results indicate novel mechanism which molecules, modulate via interactions receptor.