THE DISTRIBUTION OF LOW-THRESHOLD TTX-RESISTANT NA+ CURRENTS IN RAT TRIGEMINAL GANGLION CELLS

The distribution of low-threshold tetrodotoxin-resistant (TTX-r) Na+ current and its co-expression with high-threshold TTX-r Na+ current were studied in randomly selected acutely dissociated rat trigeminal ganglion (non-identified TG cells) and TG cells serving the temporomandibular joint (TMJ-TG cells). Conditions previously shown to enhance Na(V)1.9 channel-mediated currents (holding potential (HP) -80 mV, 130-mM fluoride internally) were employed to amplify the low-threshold Na+ current. Under these conditions, detectable low-threshold Na+ current was exhibited by 16 out of 21 non-identified TG cells (average, 1810 +/- 358 pA), and by nine of 14 TMJ-TG cells (average, 959 +/- 525 pA). The low-threshold Na+ current began to activate around -55 mV and was inactivated by holding TG cells at -60 mV and delivering 40-ms test potentials (TPs) to 0 mV. The inactivation was long lasting, recovering only 8 +/- 3% over a 5-min period after the HP was returned to -80 mV. Following low-threshold Na+ current inactivation, high-threshold TTX-r Na+ current, evoked from HP -60 mV, was observed. High-threshold Na+ current amplitude averaged 16,592 +/- 3913 pA for TPs to 0 mV, was first detectable at an average TP of -34 +/- 1.3 mV, and was 1/2 activated at -7.1 +/- 2.3 mV. In TG cells expressing prominent low-threshold Na+ currents, changing the external solution to one containing 0 mM Na+ reduced the amount of current required to hold the cells at -80 mV through -50 mV, the peak effect being observed at HP -60 mV. TG cells recorded from with a more physiological pipette solution containing chloride instead of fluoride exhibited small low-threshold Na+ currents, which were greatly increased upon superfusion of the TG cells with the adenylyl cyclase (AC) activator forskolin. These data suggest two hypotheses: (1) low- and high-threshold Na(V)1.9 and Na(V)1.8 channels, respectively, are frequently co-expressed in TG neurons serving the TMJ and other structures, and (2), Na(V)1.9 channel-mediated currents are small under physiological conditions, but may be enhanced by inflammatory mediators that increase AC activity, and may mediate an inward leak that depolarizes TG neurons, increasing their excitability. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.