Cold stimulation evokes exocytotic vesicle release from PC12 cells.

The mechanism of peripheral blood circulation failure by low temperatures, known as Raynaud's phenomenon, is not well understood at present. We examined the possibility that the efferent fibers of peripheral sympathetic neurons may release transmitters directly by cold sensation. PC12 cells, a culture model of sympathetic neurons, were placed at 25°C for 30 min, fixed with the tannic acid-glutaraldehyde-osmium method and observed by electron microscopy. The number of omega-shaped exocytotic vesicle figures increased significantly compared with that in the control (37°C), although it was lower than that of the positive control (high potassium stimulation at 25°C and 37°C). As it is known that PC12 cells and sympathetic neurons do not express the typical cold sensing channels (TRPA1 and TRPM8), our results suggest that the peripheral sympathetic neurons may have an unknown cold monitoring system which reacts to low temperatures, release transmitters by exocytosis and directly regulate local blood circulation.