Absence of an association between axotomy-induced changes in sodium currents and excitability in DRG neurons from the adult rat

Abstract

It is generally believed that nerve injury results in neuronal hyperexcitability that reflects in part a change in Na + currents. However, there are conflicting data on the nature of Na + current changes and the association between alterations in Na + currents and increases in excitability. One potential source of conflicting data is that injured and spared neurons may respond differently to nerve injury; these subpopulations of neurons have not been distinguished in previous studies with the axotomy model of nerve injury (complete transection of the sciatic nerve). The present study was performed to determine the relationship between changes in Na + channels and changes in neuronal excitability in identified injured dorsal root ganglion neurons post-axotomy. Small (<45 pF) neurons labeled with a DiI injection into the sciatic nerve were studied 10 days and 4 weeks post-axotomy. Ten days post-axotomy, tetrodotoxin-resistant (TTX-R) Na + current ( I Na) was decreased and TTX-sensitive (TTX-S) I Na was increased, however, excitability was unchanged. Four weeks post-axotomy, neurons had become hyperexcitable while TTX-R I Na remained reduced and TTX-S I Na had returned to control levels. Thus, axotomy-induced changes in Na + currents were not correlated with an axotomy-induced change in excitability. Additional analysis of axotomized neurons suggested that concomitant changes in other ionic currents occurred. These results suggest that neuronal excitability following axotomy is dependent on the sum of changes in ionic currents, and the overall effect on excitability may not always correspond to that predicted by a change in a single class of voltage-gated ion channel.