INTRACELLULAR FREE CALCIUM RESPONSES TO PROTONS AND CAPSAICIN IN CULTURED TRIGEMINAL NEURONS

Acidic solutions and capsaicin are selective chemical stimuli for noci ceptive neurons. The effect of these stimuli on intracellular calcium concentration was analysed in cultured trigeminal neurons of newborn r abbits. Rapid reductions in pH (from 7.4 to 5) evoked a transient rise in intracellular calcium concentration of 270% on average over the ba sal level (162.5 +/- 3.5 nM; n = 174) in 86% of the neurons. Maximal r esponses were found at pH 5.5. Proton-induced transients were diminish ed or abolished by 20 mM CaCl2, by zero CaCl2 and by 1 mu M Ruthenium Red. In response to 1 mu M capsaicin, 40% of the cells that were sensi tive to protons also increased their intracellular calcium concentrati on to 218% of control. Capsaicin-induced intracellular calcium concent ration rises were composed of an initial peak followed by a second, sl ower intracellular calcium concentration elevation. The capsaicin resp onse was completely blocked by 1 mu M Ruthenium Red, and disappeared i n zero calcium, but was augmented in high extracellular calcium. Intra cellular calcium concentration responses to capsaicin were still obser ved in neurons whose response to protons was desensitized by sustained exposure to low pH (pH 6.5). Cells surviving a 10-24 h capsaicin (10 mu M) treatment, still displayed responses to pH reductions. These res ults suggest that intracellular calcium concentration rises induced by moderate reductions in; pH(0) and capsaicin occur through different m echanisms.