Na(v)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 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.
Renganathan
M
M
Department of Neurology, Yale Medical School, New Haven, CT 06510, USA.
Dib-Hajj
S
S
Waxman
S G
SG
D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000378:metabolism
D021122:Protein Subunits; D015222:Sodium Channels; D002104:Cadmium; D013779:Tetrodotoxin