Mutual influence of plasma membrane structures and intracellular calcium stores on the formation of calcium signals in primary nociceptive neurons

The participation of different calcium-regulating mechanisms in the formation of intracellular calcium signals in sensory neurons was studied using two-wavelength fluorescent microscopy. Mitochondria were shown to be the most powerful intracellular calcium-regulating structures in the investigated neurons. These organelles were involved in modulation of calcium signals induced either by Ca2+ entry from the extracellular medium or by Ca2+ release from ER. Analysis of the mitochondrial calcium exchange showed that the efficiency of mitochondria depended on whether calcium entered the cytosol from ER or from the extracellular solution. Depletion of ER by activation of ryanodine-sensitive, inositol-3-phosphate-sensitive receptors of ER or by activation of the leak channels via the block of ATPases in ER activated the store-operated calcium entry from the extracellular medium to cytosol. The kinetics of the rising phase of these Ca2+ transients depended on the way of ER depletion. This allows suggesting the existence of different activation mechanisms of the investigated signals. The block of the mitochondrial calcium uniporter resulted in a fast recovery of the intracellular calcium concentration after the Ca2+ transient induced by store-operated calcium influx. We conclude that mitochondrial calcium uptake can prevent calcium-dependent inactivation of store-operated calcium channels.