Reduction in Potassium Currents in Identified Cutaneous Afferent Dorsal Root Ganglion Neurons After Axotomy

Abstract

Potassium currents have an important role in modulating neuronal excitability. We have investigated the effects of axotomy on three voltage-activated K+ currents, one sustained and two transient, in cutaneous afferent dorsal root ganglion (DRG) neurons. Fourteen to 21 days after axotomy, L4 and L5 DRG neurons were acutely dissociated and were studied 2–8 h after plating. Whole cell patch-clamp recordings were obtained from identified cutaneous afferent neurons (46–50 μm diam); K+ currents were isolated by blocking Na+ and Ca2+ currents with appropriate ion replacement and channel blockers. Separation of the current components was achieved on the basis of sensitivity to dendrotoxin or 4-aminopyridine and by the response to variation in conditioning voltage. Both control and injured neurons displayed qualitatively similar complex K+ currents composed of distinct kinetic and pharmacological components. Three distinct K+ current components, a sustained ( I K) and two transient ( I A and I D), were identified in variable proportions. However, total peak current was reduced by 52% in the axotomized cells when compared with control cells. Two current components were reduced after ligation, I Aby 60%, I K by over 65%, compared with control cells. I D appeared unaffected after acute ligation. These results indicate a large reduction in overall K+ current, resulting from reductions in I K and I A, on large cutaneous afferent neurons after nerve ligation and have implications for excitability changes of injured primary afferent neurons.