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• Zheng, T
• Uryu, N
• Ogata, N
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• Zheng, T
• Uryu, N
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• Zheng, T
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• Ogata, N

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Mar. Drugs 2010, 8(3), 728-740; doi:10.3390/md8030728

Article

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

Jun-ichi Kakimura ^1,2,* , Taixing Zheng ² , Noriko Uryu ²  and Nobukuni Ogata ^2,*

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.

Received: 15 January 2010; in revised form: 8 February 2010 / Accepted: 18 March 2010 / Published: 19 March 2010

(This article belongs to the Special Issue Tetrodotoxin)

Download PDF Full-Text [231 KB, uploaded 19 March 2010 11:30 CET]

Abstract: Sensory neurons in the dorsal root ganglion express two kinds of tetrodotoxin resistant (TTX-R) isoforms of voltage-gated sodium channels, Na_V1.8 and Na_V1.9. These isoforms play key roles in the pathophysiology of chronic pain. Of special interest is Na_V1.9: our previous studies revealed a unique property of the Na_V1.9 current, i.e., the Na_V1.9 current shows a gradual and notable up-regulation of the peak amplitude during recording (“spontaneous augmentation of Na_V1.9”). However, the mechanism underlying the spontaneous augmentation of Na_V1.9 is still unclear. In this study, we examined the effects of protein kinases A and C (PKA and PKC), on the spontaneous augmentation of Na_V1.9. The spontaneous augmentation of the Na_V1.9 current was significantly suppressed by activation of PKA, whereas activation of PKA did not affect the voltage dependence of inactivation for the Na_V1.9 current. On the contrary, the finding that activation of PKC can affect the voltage dependence of inactivation for Na_V1.9 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 Na_V1.9 was regulated directly by PKA, and indirectly by PKC.

Keywords: Na⁺ channel; tetrodotoxin; dorsal root ganglion; patch clamp; PKA; PKC

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