Mitochondrial participation in modulation of calcium transients in DRG neurons.

The effects of the mitochondrial Na+/Ca2+ exchange blocker tetraphenylphosphonium (TPP+) and the permeability transition blocker cyclosporinA (CysA) on the ability of mitochondria to participate in the regulation of intracellular calcium were investigated on freshly isolated mice sensory DRG neurons. The free intracellular calcium level (Ca2+]in) was measured using indo-1 based microfluorimetry. The characteristics of depolarization-induced Ca2+]in transients were changed in the presence of 25 microM TPP+. The amplitude of Ca2+]in transients became decreased and the restoration of resting Ca2+]in level speeded up in the presence of TPP+. Application of 5 microM cyclosporinA induced substantial residual elevation of Ca2+]in after termination of depolarization. We conclude that the mitochondrial Na+/Ca2+ exchanger mechanism plays an important role in the regulation of calcium signals during neuronal activity, prolonging them by releasing Ca2+ stored during transient peak. Activation of permeability transition pores does not participate in these processes.