Chronic treatment with ngf induces spontaneous fluctuations of intracellular Ca2+ in icilin-sensitive dorsal root ganglion neurons of the rat

Abstract

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 Ca2+ concentrations ([Ca2+]i). In the present study, the Ca2+ sources of the [Ca2+]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 [Ca2+]i were observed. The [Ca2+]i fluctuations were inhibited by Ca2+ removal or inhibitors of voltage-gated Ca2+ 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 [Ca2+]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 [Ca2+]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 Ca2+ influx through voltage-gated Ca2+ channels is the major source contributing to the [Ca2+]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.