Abstract
The movement of water across the cell membrane is a natural biological process that occurs during growth, cell division, and cell death. Many cells are known to regulate changes in their cell volume through inherent compensatory regulatory mechanisms. Cells can sense an increase or decrease in their cell volume, and compensate through mechanisms known as a regulatory volume increase (RVI) or decrease (RVD) response, respectively. The transport of sodium, potassium along with other ions and osmolytes allows the movement of water in and out of the cell. These compensatory volume regulatory mechanisms maintain a cell at near constant volume. A hallmark of the physiological cell death process known as apoptosis is the loss of cell volume or cell shrinkage. This loss of cell volume is in stark contrast to what occurs during the accidental cell death process known as necrosis. During necrosis, cells swell or gain water, eventually resulting in cell lysis. Thus, whether a cell gains or loses water after injury is a defining feature of the specific mode of cell death. Cell shrinkage or the loss of cell volume during apoptosis has been termed apoptotic volume decrease or AVD. Over the years, this distinguishing feature of apoptosis has been largely ignored and thought to be a passive occurrence or simply a consequence of the cell death process. However, studies on AVD have defined an underlying movement of ions that result in not only the loss of cell volume, but also the activation and execution of the apoptotic process. This review explores the role ions play in controlling not only the movement of water, but the regulation of apoptosis. We will focus on what is known about specific ion channels and transporters identified to be involved in AVD, and how the movement of ions and water change the intracellular environment leading to stages of cell shrinkage and associated apoptotic characteristics. Finally, we will discuss these concepts as they apply to different cell types such as neurons, cardiomyocytes, and corneal epithelial cells.
Highlights
Cell survival depends on maintaining cellular stability from altered environmental conditions that occur from both inside and outside the cell
What drives the homeostatic balance of many biological systems is the movement of monovalent ions that results in a change in water content to alter the concentration of glucose, acids/bases, and calcium
Even in death, cells attempt to maintain some sense of biological homeostasis by undergoing a programmed cell death process known as apoptosis
Summary
Cell survival depends on maintaining cellular stability from altered environmental conditions that occur from both inside and outside the cell. There have been 34 different modes of cell death described in the literature (Liu et al, 2018b) This includes the orderly degradation and recycling of cellular components known as autophagy; an ischemic cell death resulting from ATP depletion known as oncosis; death of anchorage-dependent cells that detach from the surrounding extracellular matrix known as anoikis; and a programmed mode of necrotic cell death in fibroblasts known as nemosis. While many of these modes of cell death are similar in nature, they can provide a unique characterization of the physiology in a clinical or pathological setting. We will focus on the classical physiological mode of cell death, apoptosis; and examine cell death in several cell type model systems in regards to ion and water movement that results in the loss of cell volume
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