抄録
Sensory neurons in dorsal root ganglion (DRG) express two kinds of tetrodotoxin resistant isoforms of the voltage-gated sodium channel, NaV1.8 (SNS) and NaV1.9 (NaN). These tetrodotoxin-resistant isoforms play key roles in pathophysiology of chronic pain. Of special interest is NaV1.9, which is preferentially expressed in small DRG neurons. NaV1.9 mediates a persistent sodium current, which shows an extremely slow time course distinct from the sodium current mediated by NaV1.8. Previously, we reported the unique properties of the sodium current mediated by NaV1.9 (ITTX-R/persistent) in neurons from NaV1.8-null mutant mice, i.e., ITTX-R/persistent recorded under whole-cell patch-clamp condition showed an explosive up-regulation of the peak amplitude of the current (“kindling” of ITTX-R/persistent) during recording. However, the mechanism underlying the kindling of ITTX-R/persistent is still unclear. Intracellular ATP (3 mM) and GTP (500 μM) significantly suppressed the kindling of ITTX-R/persistent. The effect of ATP was more potent than the effect of GTP. In these cases, the shift of the steady-state inactivation was not observed. A PKC activator, PMA (10 nM) also inhibited the kindling of ITTX-R/persistent. In the presence of a PKC inhibitor, Calphostin C, the effect of PMA was not observed. In addition, PMA shifted the steady-state inactivation. These results suggest that the functional expression of ITTX-R/persistent may be strongly affected by a change in intracellular conditions. [Jpn J Physiol 55 Suppl:S129 (2005)]
