Neuronal cells undergo significant fluxes in sodium and potassium during electrical signaling. When neuronal model system PC12 cells are exposed to high levels of sodium or potassium chloride for several minutes, their neurites retract into the soma. Neurite retraction is driven by membrane tension changes that result from water and ion flux through sodium, potassium, and chloride channels. Blocking these channels or increasing the osmolarity using other osmolytes does not induce retraction. During this retraction, excess membrane will be shed from the cell in the form of extracellular vesicles (EVs). EV release occurs under all tested hyperosmotic conditions, not only those that induce retraction. Dynamic light scattering shows that EVs range in size from approximately 30–300 nm in diameter. ELISA testing shows the presence of CD81, a hallmark protein of EVs. Additionally, total lipid quantification supports the identity of the isolated particles as EVs. The physiological purpose of EVs was studied by adding the EVs to naïve neuronal and muscle cells and observing the cells over three days. Retraction induced EVs appear similar in size to other hyperosmotic stress (e.g., MgSO 4 ) induced EVs, suggesting that it is membrane changes that occur in response to hyperosmotic conditions, rather than retraction, which drives the EV release. Retraction and the release of extracellular vesicles are a unique form of neuronal signaling, and understanding these events can lead to a more complete understanding of diseases caused by cellular miscommunication.
Schmidt et al. (Sun,) studied this question.