Properties of voltage-gated calcium currents in axotomized adult rat cutaneous afferent neurons.

摘要

The effect of sciatic nerve injury on the somatic expression of voltage-gated calcium currents in adult rat cutaneous afferent dorsal root ganglion (DRG) neurons identified via retrograde Fluoro-Gold labeling was studied using whole-cell patch-clamp techniques. Cutaneous afferents were classified as 'type 1' or 'type 2' according to the calcium current phenotype observed in acutely dissociated neurons: type 1 cells expressed only high voltage-activated (HVA) calcium currents while type 2 neurons possessed both high- and low voltage-activated (LVA) currents. Following a unilateral ligation and transection of the sciatic nerve, a reduction in the density of whole-cell calcium current was observed in type 1, but not type 2, neurons following nerve injury. Separation of the type 1 cells into different size classes based on measurements of cell capacitance suggests that the reduction in the voltage-gated calcium current occurred selectively in the larger cutaneous afferents.; Pharmacological dissection of the HVA current into its composite subtypes was performed to determine if particular subtypes of voltage-gated calcium channels were preferentially targeted by nerve injury in large type 1 cutaneous afferent neurons. Isolation of the N- and P/Q-type components of the HVA current in the large neurons suggests a selective reduction in N-type calcium current after injury. Analysis of the type 2 neurons provided evidence that the properties of the low-threshold T-type calcium current were unaltered by axotomy.; The properties of voltage-dependent inactivation of the HVA calcium current were compared in control and axotomized populations of type 1 cutaneous afferents. The observed decrease in the HVA current density cannot be attributed to increased steady-state inactivation in the injured population, as a similar reduction was seen at more negative holding potentials. Axotomized type 1 neurons exhibited significantly faster inactivation kinetics than control neurons, although the rate of recovery from inactivation was similar in the two groups. The HVA current of large cutaneous afferents also demonstrates a depolarizing shift in the voltage-dependence of inactivation after axotomy. The present results thus indicate that sciatic nerve injury leads to a reorganization of the HVA calcium channel properties in a subset of cutaneous afferent DRG neurons.