The distribution of low-threshold TTX-resistant Na+ currents in rat trigeminal ganglion cells

Abstract

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 NaV1.9 channel-mediated currents (holding potential (HP) −80mV, 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±358pA), and by nine of 14 TMJ-TG cells (average, 959±525pA). The low-threshold Na+ current began to activate around −55mV and was inactivated by holding TG cells at −60mV and delivering 40-ms test potentials (TPs) to 0mV. The inactivation was long lasting, recovering only 8±3% over a 5-min period after the HP was returned to −80mV. Following low-threshold Na+ current inactivation, high-threshold TTX-r Na+ current, evoked from HP −60mV, was observed. High-threshold Na+ current amplitude averaged 16,592±3913pA for TPs to 0mV, was first detectable at an average TP of −34±1.3mV, and was ½ activated at −7.1±2.3mV. In TG cells expressing prominent low-threshold Na+ currents, changing the external solution to one containing 0mM Na+ reduced the amount of current required to hold the cells at −80mV through −50mV, the peak effect being observed at HP −60mV. 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 NaV1.9 and NaV1.8 channels, respectively, are frequently co-expressed in TG neurons serving the TMJ and other structures, and (2), NaV1.9 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.