title: Contribution of endoplasmic reticulum Ca2+ regulatory mechanisms to the inflammation-induced increase in the evoked Ca2+ transient in rat cutaneous dorsal root ganglion neurons.
abstract: Persistent inflammation results in an increase in the magnitude and duration of high K(+)-evoked Ca(2+) transients in putative nociceptive cutaneous dorsal root ganglion (DRG) neurons. The purpose of the present study was to determine whether recruitment of Ca(2+)-induced Ca(2+) release (CICR) contributes to these inflammation-induced changes. Acutely dissociated, retrogradely labeled cutaneous DRG neurons from naïve and complete Freund's adjuvant inflamed adult male Sprague-Dawley rats were studied with ratiometric microfluorimetry. Ryanodine only attenuated the duration but not magnitude of the high K(+)-evoked Ca(2+) transient in neurons from inflamed rats. However, there was no significant impact of inflammation on the potency or efficacy of ryanodine-induced block of the caffeine-evoked Ca(2+) transient, or the impact of sarco-endoplasmic reticulum ATPase (SERCA) inhibition on the high K(+)-evoked Ca(2+) transient. Furthermore, while there was no change in the magnitude, an inflammation-induced increase in the duration of the caffeine-evoked Ca(2+) transient was only observed with a prolonged caffeine application. In contrast to the high K(+)-evoked Ca(2+) transient, there was no evidence of direct mitochondrial involvement or that of the Ca(2+) extrusion mechanism, the Na(+)/Ca(2+) exchanger, on the caffeine-evoked Ca(2+) transient, and block of SERCA only increased the duration of this transient. These results indicate the presence of Ca(2+) regulatory domains in cutaneous nociceptive DRG neurons within which cytosolic Ca(2+) increased via influx and release are highly segregated. Furthermore, our results suggest that changes in neither CICR machinery nor the coupling between Ca(2+) influx and CICR are primarily responsible for the inflammation-induced changes in the evoked Ca(2+) transient.
authors: Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors: Nicole N
authors: NN
authors: Scheff
authors: Shao-Gang
authors: SG
authors: Lu
authors: Michael S
authors: MS
authors: Gold
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D012867:Skin / Q000294:innervation*
chemical_list: D012433:Ryanodine; D002110:Caffeine; D005620:Freund's Adjuvant; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
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