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KMID : 1034820180140040409
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Molecular & Cellular Toxicology
2018 Volume.14 No. 4 p.409 ~ p.416
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Differential use-dependent inactivation of Nav1.8 in the subpopulation of cultured dorsal root ganglion
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Kim Dong-Hyun
Choi Jin-Sung
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Abstract
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Backgrounds: Sodium channel Nav1.8 is expressed preferentially in members of the peripheral nervous system such as nociceptive dorsal root ganglion (DRG) neurons.
Methods: Using immunocytochemistry and eletrophysiological recording, we found that a subpopulation of small DRG neurons, grouped by isolectin B4 (IB4) immunoreactivity, showed a different use-dependent inactivation of Nav1.8 current, and this situation changed over time during in vitro culture.
Results: The IB 4 - immunoreactivity of DRG neurons was not changed during in vitro culture with the exception of this small population of IB4-negative small-diameter DRG neurons. The Nav1.8 channel in IB 4 + neurons underwent a level of use-dependent inactivation that was significantly stronger than that seen in IB 4 - neurons at 1 and 2 days-in-vitro (DIV). The use-dependent inactivation of the Nav1.8 channel in IB 4 + neurons at 1 DIV was significantly attenuated at 2 DIV. The values for voltage dependency of activation and steady-state inactivation of Nav1.8 were similar in all subpopulations of DRG neurons and did not change over time. The time constant for entry into slow inactivation of Nav1.8 in IB 4 + neurons was significantly faster than in IB 4 - neurons at 1 and 2 DIV, while the rate of recovery from slow inactivation of Nav1.8 in IB 4 + neurons was slower than that seen in IB 4 - neurons. Moreover, the time constant for entry into the slow inactivation of Nav1.8 in IB 4 + neurons after 1 DIV was significantly faster than at 2 DIV, and the rate of recovery from the slow inactivation of Nav1.8 in IB 4 + neurons at 1 DIV was slower than that at 2 DIV, which indicated that the strong use-dependent inactivation in IB 4 + neurons at 1 DIV was the result of a greater preference for the slow inactivation state than at 2 DIV.
Conclusion: Our data suggest that the time-dependent change of the use-dependent inactivation of the Nav1.8 channel in DRG neurons cultured in vitro would contribute to the excitability of a subpopulation of DRG neurons and could play an important role in the development of inflammatory and neuropathic pain.
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KEYWORD
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Pain, Voltage-gated sodium channel, IB4-immunoreactivity, DRG, Nociceptor
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