Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons.
BACKGROUND
We have previously shown that a decrease of inward Ca(2+) 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 Ca(2+) level was increased to promote I(Ca), the after-hyperpolarization was decreased and repetitive firing was suppressed, which also followed amplification of Ca(2+)-activated K(+) current with selective agents NS1619 and NS309. A decreased external bath Ca(2+) 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 Ca(2+) flux, and that measures to restore I(Ca) may potentially be therapeutic for painful peripheral neuropathy.
Hogan
Quinn
Q
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. qhogan@mcw.edu
Lirk
Philipp
P
Poroli
Mark
M
Rigaud
Marcel
M
Fuchs
Andreas
A
Fillip
Patrick
P
Ljubkovic
Marko
M
Gemes
Geza
G
Sapunar
Damir
D
D000818:Animals; D001522:Behavior, Animal; D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000196:embryology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology; D011188:Potassium / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000473:pathology
C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D001562:Benzimidazoles; D007211:Indoles; D010091:Oximes; C086491:NS 1619; D011188:Potassium; D002118:Calcium