Painful nerve injury increases plasma membrane Ca2+-ATPase activity in axotomized sensory neurons.
BACKGROUND
The plasma membrane Ca2+-ATPase (PMCA) is the principal means by which sensory neurons expel Ca2+ and thereby regulate the concentration of cytoplasmic Ca2+ and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca2+ levels and activity-induced cytoplasmic Ca2+ accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain.


RESULTS
PMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca2+ sequestration with thapsigargin, and cytoplasmic Ca2+ concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca2+ transients resolved was increased in axotomized neurons after spinal nerve ligation, indicating accelerated PMCA function. Electrophysiological recordings showed that blockade of PMCA by vanadate prolonged the action potential afterhyperpolarization, and also decreased the rate at which neurons could fire repetitively.


CONCLUSIONS
We found that PMCA function is elevated in axotomized sensory neurons, which contributes to neuronal hyperexcitability. Accelerated PMCA function in the primary sensory neuron may contribute to the generation of neuropathic pain, and thus its modulation could provide a new pathway for peripheral treatment of post-traumatic neuropathic pain.
Medical College of Wisconsin, Department of Anesthesiology, Milwaukee, WI 53226, USA.
Geza
G
Gemes
Katherine D
KD
Oyster
Bin
B
Pan
Hsiang-En
HE
Wu
Madhavi Latha Yadav
ML
Bangaru
Qingbo
Q
Tang
Quinn H
QH
Hogan
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019771:Axotomy; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D048429:Cell Size / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D019284:Thapsigargin / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D053499:Plasma Membrane Calcium-Transporting ATPases; C506955:Atp2b1 protein, rat; D002118:Calcium