Restoration of Calcium Influx Corrects Membrane Hyperexcitability in Injured Rat Dorsal Root Ganglion Neurons

Abstract

BACKGROUND: We have previously shown that a decrease of inward Ca²⁺ flux (I_Ca) across the sensory neuron plasmalemma, such as happens after axotomy, increases neuronal excitability. From this, we predicted that increasing I_Ca in injured neurons should correct their hyperexcitability. METHODS: The influence of increased or decreased I_Ca upon membrane biophysical variables and excitability was determined during recording from A-type neurons in nondissociated dorsal root ganglia after spinal nerve ligation using an intracellular recording technique. RESULTS: When the bath Ca²⁺ level was increased to promote I_Ca, the after-hyperpolarization was decreased and repetitive firing was suppressed, which also followed amplification of Ca²⁺-activated K⁺ current with selective agents NS1619 and NS309. A decreased external bath Ca²⁺ concentration had the opposite effects, similar to previous observations in uninjured neurons. CONCLUSIONS: These findings indicate that at least a part of the hyperexcitability of somatic sensory neurons after axotomy is attributable to diminished inward Ca²⁺ flux, and that measures to restore I_Ca may potentially be therapeutic for painful peripheral neuropathy.