• M Renganathan, S Dib-Hajj, and S G Waxman.
• Department of Neurology, Yale Medical School, New Haven, CT 06510, USA.
• Brain Res. Mol. Brain Res. 2002 Oct 15; 106 (1-2): 70-82.

AbstractIn 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 microM) of the third TTX-R Na(+) current is significantly lower than those of Na(v)1.8 and Na(v)1.9 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(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.

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