Axotomy-induced expression of calcium-activated chloride current in subpopulations of mouse dorsal root ganglion neurons

Whole cell patch-clamp recordings of calcium-activated chloride current [I-Cl(Ca)] were made from adult sensory neurons of naive and axotomized mouse L-4-L-6 lumbar dorsal root ganglia after 1 day of culture in vitro. A basal I-Cl(Ca) was specifically expressed in a subset of naive medium-diameter neurons (30-40 mum). Prior nerve injury, induced by sciatic nerve transection 5 days before experiments, increased both I-Cl(Ca) amplitude and its expression in medium-diameter neurons. Moreover, nerve injury also induced I-Cl(Ca) expression in a new subpopulation of neurons, the large-diameter neurons (40-50 mum). Small-diameter neurons (inferior to 30 mum) never expressed I-Cl(Ca). Regulated I-Cl(Ca) expression was strongly correlated with injury-induced regenerative growth of sensory neurons in vitro and nerve regeneration in vivo. Cell culture on a substrate not permissive for growth, D,L-polyornithine, prevented both elongation growth and I-Cl(Ca) expression in axotomized neurons. Regenerative growth and the induction of I-Cl(Ca) expression take place 2 days after injury, peak after 5 days of conditioning in vivo, slowly declining thereafter to control values. The selective expression of I-Cl(Ca) within medium- and large-diameter neurons conditioned for rapid, efficient growth suggests that these channels play a specific role in postinjury behavior of sensory neuron subpopulations such as neuropathic pain and/or axonal regeneration.