Shishkin V. Interaction of calcium-regulating structures in primary sensory neurones in normal state and under different pathological conditions

The dissertation is dedicated to the investigation of intracellular calcium signalling in DRG neurons in normal state and under pathological conditions, such as diabetes and inflammation. Using mitochondrial uncoupler CCCP and Na+/Ca2+-exchanger blocker ТРР+ we demonstrated participation of mitochondria in fast uptake of Ca2+ and subsequent release to the cytosol during depolarization-induced calcium transient. It was found that mitochondria did not modulate the amplitude of [Ca2+]i transients evoked by caffeine. Mitochondrial participation in calcium uptake and release during caffeine-induced Ca2+ release was not prominent. We uncovered significant changes in Ca2+ signalling in DRG neurones under diabetes. We concluded that diabetes is associated with substantial decrease of mitochondrial Ca2+ uptake in small DRG neurones and release into the cytosol in both types of neurones. It was shown that inflammation is associated with similar changes in calcium homeostasis. It seems likely that given changes is the most important reason of the abnormalities in neuronal sensitivity and pain syndromes under diabetes and inflammation.