Na v1.5 underlies the ‘third TTX-R sodium current’ in rat small DRG neurons

Abstract

In addition to slow-inactivating and persistent TTX-R Na + currents produced by Na v1.8 and Na v1.9 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 v1.8 and Na v1.9 Na + currents. The estimated TTX K i (2.11±0.34 μM) of the third TTX-R Na + current is significantly lower than those of Na v1.8 and Na v1.9 Na + currents. The Cd 2+ sensitivity of third TTX-R Na + current is closer to cardiac Na + currents. A concentration of 1 mM Cd 2+ is required to completely block this current, which is significantly lower than the 5 mM required to block Na v1.8 and Na v1.9 currents. The third TTX-R Na + channel is not co-expressed with Na v1.8 and Na v1.9 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 v1.5 and RT-PCR and restriction enzyme polymorphism analysis, show a parallel pattern of expression of Na v1.5 in DRG during development. Taken together, these results demonstrate that Na v1.5 is expressed in a developmentally regulated manner in DRG neurons and suggest that Na v1.5 Na + channel produces the third TTX-R current.