Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia

Matsutomi Tomoya

Nakamoto Chizumi

Zheng Taixing

Kakimura Jun-ichi

Ogata Nobukuni

Pflugers Archiv : European Journal of Physiology

Small (< 25 μm in diameter) neurons of the dorsal root ganglion (DRG) express multiple voltage-gated Na+ channel subtypes, 2 of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na+ current with distinct kinetic property. However, it is not known how each type of Na+ channels contributes to the generation of action potentials in small DRG neurons. Therefore, we investigated the correlation between Na+ currents in voltage-clamp recordings and corresponding action potentials in current-clamp recordings, using wild-type (WT) and NaV1.8 knock-out (KO) mice, to clarify action potential electrogenesis in small DRG neurons. We classified Na+ currents in small DRG neurons into three categories on the basis of TTX sensitivity and kinetic properties i.e., TTX-sensitive (TTX-S)/fast Na+ current, TTX-resistant (TTX-R)/slow Na+ current and TTX-R/persistent Na+ current. Our concurrent voltage-clamp and current-clamp recordings from the same neuron revealed that action potentials in WT small DRG neurons were mainly dependent on TTX-R/slow Na+ current mediated by NaV1.8. Surprisingly, a large portion of TTX-S/fast Na+ current was switched off in WT small DRG neurons due to a hyperpolarizing shift of the steady-state inactivation (h∞), whereas in KO small DRG neurons which are devoid of TTX-R/slow Na+ current, action potentials were generated by TTX-S/fast Na+ current possibly through a compensatory shift of h∞ in the positive direction. We also confirmed that TTX-R/persistent Na+ current mediated by NaV1.9 actually regulate subthreshold excitability in small DRG neurons. In addition, we demonstrated that TTX-R/persistent Na+ current can carry an action potential when the amplitude of this current was abnormally increased. Thus, our results indicate that the action potentials in small DRG neurons are generated and regulated with a combination of multiple mechanisms that may give rise to unique functional properties of small DRG neurons.

Na+ channel

Dorsal root ganglion

Tetrodotoxin

Patch clamp

Action potential

Gating

Pain

Medical sciences [ 490 ]

eng

Springer

Copyright (c) 2006 Springer-Verlag. "The original publication is available at www.springerlink.com"

[ISSN] 0031-6768

[DOI] 10.1007/s00424-006-0104-3

[NCID] AA00771833

[PMID] 16838161

[DOI] http://dx.doi.org/10.1007/s00424-006-0104-3 isVersionOf