Analysis of the variation in use-dependent inactivation of high-threshold tetrodotoxin-resistant sodium currents recorded from rat sensory neurons

Tripathi, Pushpendra Kumar; Trujillo, Luis; Cardenas, Carla G.; Armendi, Alberto J. de; Scroggs, Reese S.

doi:10.1016/j.neuroscience.2006.08.052

Cited by 25 publications

(22 citation statements)

References 74 publications

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“…Probably, the greater than expected decrease in whole-cell Na + current was the result of the accumulation of slow inactivation of high-threshold TTXr Na + channels. Even though typical steady-state inactivation experiments indicate maximum availability for Na V 1.8 channels at À60 mV, changing the HP from À80 mV to À60 mV enhances use-dependent slow inactivation of these channels Tripathi et al, 2006).…”

Section: (F) Plot Of I H Amplitude Versus Whole-cell Capacitance For mentioning

confidence: 95%

The distribution of low-threshold TTX-resistant Na+ currents in rat trigeminal ganglion cells

Scroggs

2012

Neuroscience

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Section: (F) Plot Of I H Amplitude Versus Whole-cell Capacitance For mentioning

confidence: 95%

The distribution of low-threshold TTX-resistant Na+ currents in rat trigeminal ganglion cells

Scroggs

2012

Neuroscience

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“…Inset: stimulation protocol. leading to decrease in threshold, increase in repetitive firing, burst firing and reduction of conductance block (Baker 2005;Blair and Bean 2003;Maingret et al 2008;Tripathi et al 2006). The resulting overall increase in nociceptive output likely contributes to TNF-␣-mediated increase in excitability.…”

Section: Table 3 Values and Statistical Analysis Of Differences In Mmentioning

confidence: 99%

The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

Gudes

Barkai

Caspi

et al. 2015

Journal of Neurophysiology

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Tetrodotoxin-resistant (TTX-r) sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression levels of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptive neurons and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor-α (TNF-α), is secreted during inflammation and is associated with the early onset, as well as long-lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNF-α-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNF-α leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNF-α rapidly and substantially increases nociceptive excitability in vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent increase in TTX-r sodium currents by showing that TNF-α via p38 MAPK leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNF-α also in a p38 MAPK-dependent manner increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in the mediated nociceptive hyperexcitability of TNF-α during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes.

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“…The midpoint of TTX-R slow inactivation is actually more hyperpolarized than that for fast inactivation (Blair & Bean, 2003), in marked contrast to the reverse situation commonly found for TTX-S currents (Kuo & Bean, 1994;Fleidervish et al 1996;Fazan et al 2001). Build-up of slow inactivation is likely to be responsible for the use-dependent inhibition of TTX-R currents on repetitive stimulation (Rush et al 1998;Blair & Bean, 2003;Tripathi et al 2006) and the cell-to-cell variations in TTX-R current properties seen in these studies might reflect regulation of Na v 1.8 by calmodulin J Physiol 579.1 (Choi et al 2006). Interestingly, use-dependent slow inactivation of Na v 1.8 current is stronger and develops more rapidly in IB4+ DRG neurons, compared to IB4-DRG neurons, and recovery from slow inactivation is slower in IB4+ neurons (Choi et al 2007), adding to evidence (Stucky & Lewin, 1999;Braz et al 2005;Fang et al 2006) that these subclasses of DRG neurons are functionally distinct.…”

Section: Figure 5 Putative Roles Of Different Sodium Channel Subtypementioning

confidence: 99%

Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons

Rush

Cummins

Waxman

2007

The Journal of Physiology

376

337

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Dorsal root ganglion neurons express an array of sodium channel isoforms allowing precise control of excitability. An increasing body of literature indicates that regulation of firing behaviour in these cells is linked to their patterns of expression of specific sodium channel isoforms, which have been discovered to possess distinct biophysical characteristics. The pattern of expression of sodium channels differs in different subclasses of DRG neurons and is not fixed but, on the contrary, changes in response to a variety of disease insults. Moreover, modulation of channels by their environment has been found to play an important role in the response of these neurons to stimuli. In this review we illustrate how excitability can be finely tuned to provide contrasting firing templates in different subclasses of DRG neurons by selective deployment of various sodium channel isoforms, by plasticity of expression of these proteins, and by interactions of these sodium channel isoforms with each other and with other modulatory molecules.

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Analysis of the variation in use-dependent inactivation of high-threshold tetrodotoxin-resistant sodium currents recorded from rat sensory neurons

Cited by 25 publications

References 74 publications

The distribution of low-threshold TTX-resistant Na+ currents in rat trigeminal ganglion cells

The distribution of low-threshold TTX-resistant Na+ currents in rat trigeminal ganglion cells

The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons

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