Nav 1.5 underlies the 'third TTX-R sodium current' in rat small DRG neurons

In addition to slow-inactivating and persistent TTX-R Na+ currents produced by Na(v)1.8 and Na(v)1.9 Na+ channels, respectively, a third TTX-R Na+ current with fast activation and inactivation can be recorded in 80% of small neurons of dorsal root ganglia (DRG) from E15 rats, but in only 3% of adult small DRG neurons. The half-time for activation, the time constant for inactivation, and the midpoints of activation and inactivation of the third TTX-R Na+ currents are significantly different from those of Na(v)1.8 and Na(v)1.9 Na+ currents. The estimated TTX K-i (2.11+/-0.34 muM) of the third TTX-R Na+ current is significantly lower than those of Na(v)1.8 and Nav1.9 Na+ currents. The Cd2+ sensitivity of third TTX-R Na+ current is closer to cardiac Na+ currents. A concentration of 1 mM Cd2+ is required to completely block this current, which is significantly lower than the 5 mM required to block Na(v)1.8 and Na(v)1.9 currents. The third TTX-R Na+ channel is not co-expressed with Na(v)1.8 and Na(v)1.9 Na+ channels in DRG neurons of E18 rats, at a time when all three currents show comparable densities. The physiological and pharmacological profiles of the third TTX-R Na+ current are similar to those of the cardiac Na+ channel Na(v)1.5 and RT-PCR and restriction enzyme polymorphism analysis, show a parallel pattern of expression of Na(v)1.5 in DRG during development. Taken together, these results demonstrate that Na(v)1.5 is expressed in a developmentally regulated manner in DRG neurons and suggest that Na(v)1.5 Na+ channel produces the third TTX-R current. (C) 2002 Elsevier Science B.V. All rights reserved.