Electrophysiological characterization of the tetrodotoxin-resistant Na+ channel, Nav1.9, in mouse dorsal root ganglion neurons

Maruyama, Hiroshi; Yamamoto, Mitsuko L.; Matsutomi, Tomoya; Zheng, Taixing; Nakata, Yoshihiro; Wood, John N.; Ogata, Nobukuni

doi:10.1007/s00424-004-1315-0

Cited by 47 publications

(115 citation statements)

References 49 publications

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“…The dissociation of single DRG neurons and their culture have been described previously (12). Briefly, adult mice were sacrificed by cervical dislocation during ethylcarbamate (3 mg / g; Wako Pure Chemicals, Osaka) anesthesia.…”

Section: Isolation Of Single Drg Neurons and Cell Culturementioning

confidence: 99%

“…We defined DRG neurons that were smaller than 25 µm in diameter as small neurons (26), and small neurons thus defined were used throughout the study. We employed KO DRG neurons (6,12,13) in addition to WT DRG neurons in this study. Unless otherwise specified, the experiments were performed in neurons from WT DRG.…”

Section: +mentioning

confidence: 99%

“…We compensated for the liquid junction potential between internal and external solutions by adjusting the zero current potential to the liquid junction potential. Only cells showing an adequate voltage and space clamp (12) were used.…”

Section: +mentioning

confidence: 99%

“…Consequently, a possible involvement of I NaN has not been taken into consideration. In this study, therefore, we investigated the effect of PGE 2 on isolated I SNS or I NaN using wild-type (WT) as well as the Na V 1.8 knock-out (KO) mice (6,12,13). Unexpectedly, PGE 2 had no detectable effect on I SNS or I NaN , raising a question regarding the modulatory role of PGE 2 on TTX-R Na + current in inflammatory hyperalgesia.…”

Section: Introductionmentioning

confidence: 98%

“…The former component (which we refer to as I SNS ) activates and inactivates more slowly than TTX-sensitive Na + currents (4,5,13) and is thought to play a key role in action potential electrogenesis in small DRG neurons (7,13). The latter component (referred to as I NaN ) is characterized by extremely prolonged time courses of activation and inactivation at low activation voltages (9,12,14) and may regulate subthreshold excitability of small DRG neurons (9, 11 -13).…”

Section: Introductionmentioning

confidence: 99%

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Prostaglandin E2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na+ Current in Mouse Dorsal Root Ganglion

et al. 2007

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Abstract. One possible mechanism underlying inflammation-induced sensitization of the primary afferent neuron is the upregulation of tetrodotoxin-resistant (TTX-R) Na + current by inflammatory mediators such as prostaglandins. This notion is based on reports that showed an augmentation of TTX-R Na + current following an application of prostaglandin E 2 (PGE 2 ) in dorsal root ganglion (DRG) neurons. However, no information was available on the properties of the novel type of TTX-R Na + channel, Na V 1.9, at times when these reports were published. Hence, the contribution of Na V 1.9 to the PGE 2 -induced upregulation of TTX-R Na + current remains to be elucidated. To further examine the modulation of TTX-R Na + current by PGE 2 , we recorded two components of TTX-R Na + current in isolation from small (<25 µm in diameter) DRG neurons using wild-type and Na V 1.8 knock-out mice. Unexpectedly, neither the component mediated by Na V 1.8 nor the persistent component mediated by Na V 1.9 was affected by PGE 2 (1 and 10 µM). Our results raise a question regarding the well-known modulatory role of PGE 2 on TTX-R Na + current in inflammatory hyperalgesia.

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Section: Isolation Of Single Drg Neurons and Cell Culturementioning

confidence: 99%

Section: +mentioning

confidence: 99%

Section: +mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Prostaglandin E2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na+ Current in Mouse Dorsal Root Ganglion

et al. 2007

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Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Gawlak

Szulczyk

Berłowski

et al. 2017

Developmental Neurobiology

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Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX-resistant, low-threshold, noninactivating, and voltage-dependent Na current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017.

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Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia

Matsutomi

Nakamoto

Zheng

et al. 2006

Pflugers Arch - Eur J Physiol

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Small (<25 microm in diameter) neurons of the dorsal root ganglion (DRG) express multiple voltage-gated Na(+) channel subtypes, two of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na(+) current with distinct kinetic property. However, it is not known how each type of Na(+) channel contributes to the generation of action potentials in small DRG neurons. Therefore, we investigated the correlation between Na(+) currents in voltage-clamp recordings and corresponding action potentials in current-clamp recordings, using wild-type (WT) and Na(V)1.8 knock-out (KO) mice, to clarify the action potential electrogenesis in small DRG neurons. We classified Na(+) currents in small DRG neurons into three categories on the basis of TTX sensitivity and kinetic properties, i.e., TTX-sensitive (TTX-S)/fast Na(+) current, TTX-resistant (TTX-R)/slow Na(+) current, and TTX-R/persistent Na(+) current. Our concurrent voltage- and current-clamp recordings from the same neuron revealed that the action potentials in WT small DRG neurons were mainly dependent on TTX-R/slow Na(+) current mediated by Na(V)1.8. It was surprising that a large portion of TTX-S/fast Na(+) current was switched off in WT small DRG neurons due to a hyperpolarizing shift of the steady-state inactivation (h (infinity)), whereas in KO small DRG neurons which are devoid of TTX-R/slow Na(+) current, the action potentials were generated by TTX-S/fast Na(+) current possibly through a compensatory shift of h (infinity) in the positive direction. We also confirmed that TTX-R/persistent Na(+) current mediated by Na(V)1.9 actually regulates subthreshold excitability in small DRG neurons. In addition, we demon strated that TTX-R/persistent Na(+) current can carry an action potential when the amplitude of this current was abnormally increased. Thus, our results indicate that the action potentials in small DRG neurons are generated and regulated with a combination of multiple mechanisms that may give rise to unique functional properties of small DRG neurons.

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Electrophysiological characterization of the tetrodotoxin-resistant Na+ channel, Nav1.9, in mouse dorsal root ganglion neurons

Cited by 47 publications

References 49 publications

Prostaglandin E2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na+ Current in Mouse Dorsal Root Ganglion

Prostaglandin E2 Has No Effect on Two Components of Tetrodotoxin-Resistant Na+ Current in Mouse Dorsal Root Ganglion

Age‐dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats

Multiple types of Na+ currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia

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