PROSTAGLANDIN E-2-MEDIATED UPREGULATION OF NEUROEXCITATION AND PERSISTENT TETRODOTOXIN-RESISTANT Na+ CURRENTS IN Ah-TYPE TRIGEMINAL GANGLION NEURONS ISOLATED FROM ADULT FEMALE RATS

摘要

Prostaglandin-E-2 (PGE(2)) is a very important inflammatory mediator and PGE(2)-mediated neuroexcitation in sex-specific distribution of Ah-type trigeminal ganglion neurons (TGNs) isolated from adult female rats is not fully addressed. The whole-cell patch-clamp experiment was performed to verify the effects of PGE(2), forskolin, and GPR30-selective agonist (G-1) on action potential (AP) and tetrodotoxin-resistant (TTX-R) Na+ currents in identified Ah-type TGNs. The results showed that the firing frequency was increased in Ah- and C-types by PGE(2), which was simulated by forskolin and inhibited by Rp-cyclic adenosine monophosphate (cAMP), while G-1 mimicked this effect only in Ah-types, which was abolished by GPR30-selective antagonist (G-15). Although the amplitude of AP was increased in Ah-and C-types, increased maximal upstroke velocity was confirmed only in Ah-types, suggesting distinct alternations in current density and/or voltage-dependent property of Na+ channels. With 1.0 mu M PGE(2), TTX-R Na+ currents were upregulated without changing the current-voltage relationship and voltage-dependent activation in C-types, however, the TTX-R Na+ current was augmented in Ah-types, peaked voltage and the voltage-dependent activation were both shifted toward hyperpolarized direction with faster slope. Intriguingly, the low-threshold persistent TTX-R component was activated from -60 mV and increased almost double at -30 mV compared with similar to 30-40% increment of TTX-R component being activated at similar to-10 mV. Additionally, the change in TTX-R component of Ah-types was equivalent well with that in C-type TGNs. Taken these data together, we conclude that PGE(2) modulates the neuroexcitation via cAMP-mediated upregulation of TTX-R Na+ currents in both cell-types with hormone-dependent feature, especially persistent TTX-R Na+ currents in sex-specific distribution of myelinated Ah-type TGNs. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.