Mitochondrial calcium accumulation following activation of vanilloid (VR1) receptors by capsaicin in dorsal root ganglion neurons.
Stimulation of the vanilloid (capsaicin) receptor (VR1), currently viewed as a molecular integrator of chemical and physical noxious stimuli, evoked intracellular Ca2+ transients in a capsaicin-sensitive subpopulation of rat dorsal root ganglion neurons. These were comprised of an initial fast rise (seconds) followed by a long-lasting intracellular Ca2+ recovery (tens of minutes). The rate of intracellular Ca2+ recovery was dependent on the magnitude of intracellular Ca2+ transients. Opening of voltage-operated Ca2+ channels in the same neurons by K+ depolarization evoked intracellular Ca2+ elevation of a similar amplitude and rate of rise; however, the recovery of intracellular Ca2+ to the prestimulated level was significantly faster. A mitochondrial uncoupler (10 microM carbonyl cyanide m-chlorophenylhydrasone) was used to reveal the role of mitochondria in intracellular Ca2+ buffering. Carbonyl cyanide m-chlorophenylhydrasone-evoked elevation in intracellular Ca2+ was greater in neurons previously stimulated with capsaicin compared with KCl. Neither extracellular Ca2+ nor ATP depletion influenced significantly the carbonyl cyanide m-chlorophenylhydrasone-sensitive intracellular Ca2+ elevation in neurons loaded with Ca2+ via vanilloid 1 receptor stimulation. The effects of carbonyl cyanide m-chlorophenylhydrasone suggest that the amount of Ca2+ buffered by mitochondria is greater when extracellular Ca2+ enters the neuron via the vanilloid 1 receptor channel than via voltage-operated Ca2+ channels. The long duration of intracellular Ca2+ decline in neurons stimulated with capsaicin, which depends on the amount of Ca2+ buffered by mitochondria, may reflect a specific mechanism of Ca2+ buffering following activation the pain receptor VR1.
Dedov
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Department of Pharmacy, University of Sydney, NSW, Australia.
Roufogalis
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology*; D014475:Uncoupling Agents / Q000494:pharmacology
D011955:Receptors, Drug; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011189:Potassium Chloride; D002211:Capsaicin; D002118:Calcium