Functional roles of TTX-sensitive and TTX-resistant sodium channels in action potential generation of mouse dorsal root ganglion neurons.

Abstract

DRG neurons express 7 voltage-gated Na⁺ channel α-subunits, 5 of which being sensitive to tetrodotoxin (TTX) and the remaining 2 being resistant. These channels show preferential distribution within DRG depending on the type of neurons, mediating Na⁺ currents (I_Nas) with distinct kinetics. The preferential distribution of voltage-gated Na⁺ channels may bring about differential mechanisms of action potential generation. However, it is not known how each type of Na⁺ channels contributes to the generation of action potentials. Therefore, we investigated the correlation between I_Nas in voltage-clamp recordings and corresponding action potentials in current-clamp recordings to clarify action potential electrogenesis in DRG neurons. We classified I_Nas recorded in DRG neurons into four types on the basis of TTX sensitivity and kinetic properties. The action potentials in small DRG neurons were dependent on TTX-R/slow I_Na mediated by Na_V1.8, whereas action potentials in large DRG neurons were mediated by TTX-S/fast I_Na. TTX-S/fast I_Na was switched off in small DRG neurons due to a hyperpolarizing shift of the steady-state inactivation. We also found that TTX-R/persistent I_Na mediated by Na_V1.9 and TTX-S/persistent I_Na regulate subthreshold excitability in small and large DRG neurons, respectively. Thus, our results demonstrate that the action potentials in DRG neurons are generated and regulated with distinct mechanisms that may give rise to differential functional properties of DRG neurons. [Jpn J Physiol 55 Suppl:S129 (2005)]