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.