Capsaicin-induced depolarisation of mitochondria in dorsal root ganglion neurons is enhanced by vanilloid receptors.

Capsaicin, a pungent ingredient of hot chilli peppers, triggered Ca(2+) influx in dorsal root ganglion (DRG) neurons, which express specific vanilloid receptors of type 1, with ED(50)<100 nM. An increase in capsaicin concentration to 10 microM inhibited Ca(2+) clearance from the cytosol, but did not affect the amplitude of intracellular Ca(2+) elevation. In DRG neurons, 10 microM capsaicin also produced a significant drop in mitochondrial membrane potential (Deltapsi), as measured with the mitochondria-specific potentiometric fluorescent dye JC-1. Similar loss of mitochondrial potential upon application of capsaicin was observed in non-neuronal primary (human lymphocytes) and transformed (human myeloid leukaemia cell line, HL-60) cells. The EC(50) values for capsaicin-induced mitochondrial depolarisation were 6.9 microM (DRG neurons), 200 microM (human lymphocytes) and 150 microM (HL-60 cells). Removal of extracellular Ca(2+) or an application of the antioxidant trolox attenuated capsaicin-induced dissipation of Deltapsi in DRG neurons, but not in human lymphocytes and HL-60 cells. Rotenone, an inhibitor of complex I of the mitochondrial respiratory chain, and oligomycin, an inhibitor of F(0)F(1)-ATPase, significantly enhanced the mitochondrial depolarisation produced by capsaicin in DRG neurons. In human lymphocytes and HL-60 cells, only oligomycin potentiated the effect of capsaicin. From our results, we suggest that, in DRG neurons and non-neuronal cells, capsaicin dissipates Deltapsi, possibly due to a direct inhibition of complex I of the mitochondrial respiratory chain. The presence of vanilloid receptor-1 in DRG neurons makes their mitochondria 20-30-fold more sensitive to the depolarising effect of capsaicin compared with non-neuronal cells lacking vanilloid receptor-1. The higher sensitivity of DRG neurons to capsaicin may underlie a selective neurotoxicity of capsaicin towards sensory neurons.