Modulation by oxytocin of ATP-activated currents in rat dorsal root ganglion neurons

The modulatory effect of oxytocin (OT) on ATP-activated currents (I ATP) was studied in freshly isolated dorsal root ganglion (DRG) neurons of rats using whole cell clamp technique. In most of the neurons examined (50/70, 71.4%) extracellular application of OT (10 −9–10 −5 mol/L) suppressed I ATP while in the rest (20/70, 28.6%) no modulatory effect was observed. OT shifted the ATP concentration-response curve downwards with a decrease of 39.8±4.2% in the maximal current response and with no significant change of Kd value. This OT-induced inhibition of I ATP showed no voltage dependence, and could be blocked by [d(CH 2) 5,Tyr(Me) 2,Thr 4,Tyr-NH 2 9]-OVT (d(CH 2) 5-OVT) (10 −8 mol/L), a specific OT receptor antagonist. Intracellular application of H-9 (4×10 −5 mol/L, an inhibitor of protein kinase A) ( n=12), BAPTA (10 −2 mol/L, a chelator of calcium ions) ( n=4) could reverse the inhibitory effect of extracellular OT (10 −7 mol), while inclusion of H-7 (2×10 −5 mol/L, a protein kinase C inhibitior) ( n=8) and KN-93 (10 −5 mol/L, an inhibitor of CaMKII) ( n=9) in the recording pipette did not affect this effect. The results suggested that OT inhibition on ATP-activated currents was mediated by OT receptors in the membrane of DRG neurons; and this inhibitory effect involved the transduction of intracellular cAMP-PKA and Ca 2+.