Regulation of the Spontaneous Augmentation of Na_V1.9 in Mouse Dorsal Root Ganglion Neurons : Effect of PKA and PKC Pathways

Kakimura Jun-ichi

Zheng Taixing

Uryu Noriko

Ogata Nobukuni

Marine Drugs

Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, NaV1.8 and NaV1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is NaV1.9: our previous studies revealed a unique property of the NaV1.9 current, i.e., the NaV1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording ("spontaneous augmentation of NaV1.9"). However, the mechanism underlying the spontaneous augmentation of NaV1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of NaV1.9. The spontaneous augmentation of the NaV1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the NaV1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for NaV1.9 in the perforated patch recordings,where the augmentation does not occur, suggests that the effects of PMA are independent of the augmentation process. These results indicate that the spontaneous augmentation of NaV1.9 was regulated directly by PKA, and indirectly by PKC.

Na+ channel

Tetrodotoxin

dorsal root ganglion

patch clamp

PKA

PKC

Medical sciences [ 490 ]

eng

Molecular Diversity Preservation International-MDPI

[ISSN] 1660-3397

[DOI] 10.3390/md8030728

[NCID] AA1203626X

[DOI] http://dx.doi.org/10.3390/md8030728