Plasma membrane blebbing

Alterations in the cytoskeleton. The cytoskeleton depends on the intracellular Ca2+ concentration, which affects actin bundles, the interactions between actin and myosin and a-tubulin polymerization. The effect of increases in Ca2+ on the cytoskeletal attachments to the plasma membrane and the role of the cytoskeleton in cellular integrity have already been mentioned (see above). If the cytoskeleton is damaged or disrupted or its function altered by an increase in Ca2+, then blebs or protrusions appear on the plasma membrane (see below). As well as an increase in Ca2+, oxidation of, or reaction with sulfydryl groups, such as alkylation or arylation, for example, may disrupt the cytoskeleton, as thiols... 

Therefore, ATP levels will reach a point when the cell cannot survive, Ca2+ levels are too high, and the plasma membrane blebs and ruptures. 

This process is an early morphological change in cells often seen in isolated cells in vitro but also known to occur in vivo. The blebs, which appear before membrane permeability alters, are initially reversible. However, if the toxic insult is sufficiently severe and the cellular changes become irreversible, the blebs may rupture. If this occurs, vital cellular components may be lost and cell death follows. The occurrence of blebs may be due to damage to the cytoskeleton, which is attached to the plasma membrane as described above. The cause may be an increase in cytosolic Ca2+, interaction with cytoskeletal proteins, or modification of thiol groups (see below). 

Bellomo G, Mirabelli F, Salis A, Vairetti M, Richelmi P, Finardi G, Thor H. Orrenius S. Oxidative stress-induced plasma membrane blebbing and cytoskeletal alterations in normal and cancer cells. Ann NY Acad Sci 1988 551 128-130. 

In certain types of brain injury, such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain. This destroys the cytosketelon, causing the membrane to form blebs, irregular bulges in the plasma membrane of a cell caused by localised decoupling of the cytoskeleton from the plasma membrane, ultimately leading to degradation and usually death of the cell. 

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