Dual Modulation of Interleukin-1 Beta on Tetrodotoxin-Sensitive Sodium Currents in Mice Trigeminal Ganglion Cells by IL-1 receptor independence

摘要

Using whole-cell patch clamp technique on the membrane of freshly isolated trigeminal ganglion (TG) neurons, the effects of recombinant human interleukin-1 β (rhIL-1 β) on TTX-sensitive(TTX-S) voltage-gated sodium currents were observed to investigate its molecular mechanism in the modulation of orofacial nociceptive processing. The experimental data demonstrated that rhIL-1 β had dual effects on TTX-S sodium channels. Compared to the effects of external solution on Peak TTX-S sodium currents in TG neurons (from 100% to 104.62±4.35%), Peak TTX-S sodium currents decreased significantly after application of 1ng/mL rhIL-1 β (from 100% to 54.69±5.53%, n=14, P < 0.05) and 10ng/mL rhIL-1 β (from 100% to 79.4.±8.73%, n=9, P < 0.05) respectively, while peak TTX-sensitive(TTX-S) sodium currents increased significantly after application of 100ng/mL rhIL-1 β (from 100% to 120.96±6.72%, n=14, P < 0.05).Both inhibited effects of 1ng/mL rhIL-1 β and potentiated effects of 100ng/mL rhIL-1 β on TTX-S sodium currents showed reversible and IL-1 receptor independence. The steady-state inactivation curve shifted toward the left and the steady-state recovery curve shifted toward the right after application of 1ng/mL rhIL-1 β, while the steady-state activation curve shifted toward the left after application of 100ng/mL rhIL-1 β. The dual effects of interleukin-1 beta on TTX-S sodium currents in TG cells could partly explain its dual modulation of nociceptive processing and dual protection of neurons.