Changes in mitochondrial Ca2+ homeostasis in primary sensory neurons of diabetic mice.

Changes in neuronal Ca2+ homeostasis were studied on freshly isolated dorsal root ganglion neurons of adult control mice and mice with streptozotocin (STZ)-induced diabetes. The cytoplasmic free Ca2+ concentration ([Ca2+]in) was measured using indo-1 based microfluorimetry. The participation of mitochondria in [Ca2+]in homeostasis was determined by investigation of changes which occurred after addition of mitochondrial protonophore (CCCP) to the extracellular solution. In control cells 10 microM CCCP applied before membrane depolarization induced an increase of the amplitude of depolarization-induced [Ca2+]in transients and disappearance of their delayed recovery, indicating the participation of mitochondria in fast uptake of Ca2+ ions from the cytosol during the peak of the transient and subsequent slow release them back during its decay. In diabetic animals the increase of the peak transient amplitude under the action of CCCP became diminished in small (nociceptive) neurons and the delayed elevation of [Ca2+]in disappeared in both large and small neurons. It is concluded that in diabetic conditions substantial changes occur in the Ca2+ homeostatic functions of mitochondria, manifested by decreased Ca2+ uptake in small neurons and depressed Ca2+ release into the cytosol in all types of neurons.