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Open AccessArticle

Regulation of the Spontaneous Augmentation of NaV1.9 in Mouse Dorsal Root Ganglion Neurons: Effect of PKA and PKC Pathways

1
Technical Center, Hiroshima University, Hiroshima, 734-8551, Japan
2
Department of Neurophysiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2010, 8(3), 728-740; https://doi.org/10.3390/md8030728
Received: 15 January 2010 / Revised: 8 February 2010 / Accepted: 18 March 2010 / Published: 19 March 2010
(This article belongs to the Special Issue Tetrodotoxin 2011)
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. View Full-Text
Keywords: Na+ channel; tetrodotoxin; dorsal root ganglion; patch clamp; PKA; PKC Na+ channel; tetrodotoxin; dorsal root ganglion; patch clamp; PKA; PKC
MDPI and ACS Style

Kakimura, J.-I.; Zheng, T.; Uryu, N.; Ogata, N. Regulation of the Spontaneous Augmentation of NaV1.9 in Mouse Dorsal Root Ganglion Neurons: Effect of PKA and PKC Pathways. Mar. Drugs 2010, 8, 728-740.

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