Chronic treatment with NGF induces spontaneous fluctuations of intracellular Ca(2+) in icilin-sensitive dorsal root ganglion neurons of the rat.
Adult rat dorsal root ganglion (DRG) neurons cultured in the presence of 100 ng/ml NGF show spontaneous action potentials and fluctuations in their cytosolic Ca(2+) concentrations ([Ca(2+)](i)). In the present study, the Ca(2+) sources of the [Ca(2+)](i) fluctuations and the types of neurons whose excitability was affected by NGF were examined. In the subpopulation of NGF-treated neurons, obvious fluctuations of [Ca(2+)](i) were observed. The [Ca(2+)](i) fluctuations were inhibited by Ca(2+) removal or inhibitors of voltage-gated Ca(2+) channels. Regardless of the treatment with NGF, about half of the neurons responded to capsaicin and 10% of the neurons responded to icilin, and almost all icilin-responding neurons also responded to capsaicin. Fluctuations of [Ca(2+)](i) with large amplitudes were observed in 12 out of 131 NGF-treated neurons. Among these 12 neurons, 10 neurons responded to both capsaicin and icilin. The degree of the [Ca(2+)](i) fluctuations in the NGF-treated neurons responding to both capsaicin and icilin was significantly larger than in other neurons. These results suggest that neurons expressing both capsaicin- and icilin-sensitive TRP channels are susceptible to NGF and become hyperexcitable and that Ca(2+) influx through voltage-gated Ca(2+) channels is the major source contributing to the [Ca(2+)](i) fluctuations. Since such DRG neurons could play a physiological role as nociceptors, the NGF-induced spontaneous activity of DRG neurons may be the underlying mechanism of neuropathic pain.
Kayano
Tomohiko
T
Department of Veterinary Physiology, Tottori University, Tottori, Japan.
Kitamura
Naoki
N
Moriya
Taiki
T
Tsutsumi
Atsushi
A
Ozaki
Yui
Y
Dayanithi
Govindan
G
Shibuya
Izumi
I
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D005727:Ganglia, Spinal / Q000166:cytology*; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011744:Pyrimidinones; D020932:Nerve Growth Factor; C490483:icilin; D002211:Capsaicin; D002118:Calcium