Changes in Na⁺ Channel Currents of Rat Dorsal Root Ganglion Neurons Following Axotomy and Axotomy-Induced Autotomy

Abstract

Abdulla, Fuad A. and Peter A. Smith. Changes in Na ϩ channel currents of rat dorsal root ganglion neurons following axotomy and axotomy-induced autotomy. J Neurophysiol 88: 2518 -2529, 2002; 10.1152/jn.00913.2001. Section of rat sciatic nerve (axotomy) increases the excitability of neurons in the L 4 -L 5 dorsal root ganglia (DRG). These changes are more pronounced in animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine changes in the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) components of sodium channel currents (I Na ) that may contribute to axotomy-induced increases in excitability. Cells were initially divided on the basis of size into "large," "medium," and "small" groups. TTX-S I Na predominated in "large" cells, whereas TTX-R I Na predominated in some, but not all "small cells." "Small" cells were therefore subdivided into "smallslow" cells, which predominately exhibited TTX-R I Na and "small fast" cells that exhibited more TTX-S I Na . In contrast to results obtained in other laboratories, where slightly different experimental procedures were used, we found that axotomy increased TTX-R and/or TTX-S I Na and slowed inactivation. The effects were greatest in "small-slow" cells and least in "large" cells. The changes promoted by axotomy were expressed more clearly in animals that exhibited autotomy. Also, the presence of autotomy correlated with a shift in the properties of I Na in "large" rather than "small-slow," putative nociceptive cells. These trends parallel previous observations on axotomyinduced increases in excitability, spike height, and spike width that are also greatest in "small" cells and least in "large" cells. In addition, the presence of autotomy correlates with an increase in excitability of "large" rather than "small" cells. Increases in TTX-R and TTX-S I Na thus coincide with axotomy-induced increases in excitability and alterations in spike shape across the whole population of sensory neurons. Injury-induced changes of this type are likely associated with the onset of chronic pain in humans.

Na+ Channel Scn1b Gene Regulates Dorsal Root Ganglion Nociceptor Excitability in Vivo

“…2B. In this example, as in practically all small DRG neurons tested and in previous reports (4,18,20), the fast I Na (TTX-S) inactivated at more negative voltages than the slow I Na (TTX-R). Inactivation curves shown were generated from the same cells used to calculate activation curves in Fig.…”

“…Size-We measured C m of 20.0 Ϯ 1.6 pF (n ϭ 34) for WT and 16.28 Ϯ 0.9 pF (n ϭ 29) for null neurons (p ϭ 0.051) (4,18,19). On average, Scn1b null neurons exhibited a slightly smaller C m than WT neurons.…”

“…This experiment classified small DRG neurons into two subgroups: "small fast" and "small slow," as described previously for Scn2b null neurons (4). If the maximum amplitude of TTX-S I Na was greater than 70% of the total I Na for a given cell, that cell was placed in the small fast subgroup (4,18). These cells made up 65% (13 of 20) of the WT small cell population and 44% (10 of 23) of the Scn1b null small neurons.…”

Tetrodotoxin-resistant voltage-dependent sodium channels in identified muscle afferent neurons

“…TTX-R Na V 1.8 channels are expressed in DRG neurons (Bulaj et al 2006;Jarvis et al 2007), and we hypothesized that a large fraction of the Na V current in our TTX-R muscle afferent neurons was generated by Na V 1.8 channel activity. This hypothesis was supported by the slower activation and inactivation kinetics of the Na V current in TTX-R versus TTX-S neurons (Abdulla and Smith 2002;Blair and Bean 2002). We further tested this hypothesis by examining the effect of the Na V 1.8 blocker A803 (Jarvis et al 2007).…”

Sodium Channel β2 Subunits Regulate Tetrodotoxin-Sensitive Sodium Channels in Small Dorsal Root Ganglion Neurons and Modulate the Response to Pain

“…Total I Na , the sum of TTX-S and TTX-R I Na (Roy and Narahashi, 1992;Rush et al, 1998;Abdulla and Smith, 2002;Dib-Hajj et al, 2002), was recorded using a series of depolarizing voltage commands from a holding potential of Ϫ80 mV. To explore the voltage dependence of I Na in DRG neurons of ␤2 ϩ/ϩ and ␤2…”