L12 Cell Volume Reg 2011 - COPYRIGHT Mammalian Physiology...

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COPYRIGHT Prof. Beyenbach
Mammalian Physiology BIOAP 4580
2011
MECHANISMS OF CELL VOLUME REGULATION
1. A cell volume constant with time.
a) Diffusion distance. Single cells do not grow into giant cells because of the limits of
diffusion. Once solute and water have crossed the cell membrane, transport through the
cytoplasm depends largely on diffusion. Thus, intracellular diffusion becomes a rate-
limiting step of metabolism as cells take on size. An optimum (or perhaps limiting) cell
size is reached when diffusion adequately supports transport to the very center of the cell.
There is an additional restriction to cell size: Volume (size) increases by the power of 3
whereas surface area increases only by the power of 2 (eq. 1, 2). Thus, as cell size
(volume, V) increases it will soon outgrow the transport capacity of the cell membrane,
unless the cell surface (S) is amplified via microvilli or membrane infoldings, as in many
epithelial cells.
(eq.1)
where L is length (eq.2)
b) Preventing cell swelling and lysis in isotonic media.
“The critical event that may best be called the origin of life was the enclosure of several
self-replicating polymers within a semi- permeable membrane.” (Haldane, 1954)
The enclosure of charged impermeant molecules (proteins, enzymes) in a distensible
membrane, that is permeable to small charged solutes and water, inevitably results in
solute entry, swelling, and ultimately lysis (Fig. 1). This was first recognized by Josiah
Willard Gibbs (1839-1903) and later by Frederick George Donnan (1870-1906).
Fig. 1. The problem of negatively
charged intracellular
macromolecules to which the cell
membrane is impermeable. Since
the membrane is permeable to
diffusible cations and anions, they
will enter the cell, setting up an
oncotic pressure that eventually
will bring about lysis (lest cell
swelling is opposed by a rigid cell
wall as in plant cells, or water is
pumped out again).

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Even though the cell may be in isosmotic media it will swell as diffusible ions move to
reach Gibbs-Donnan equilibrium. However, equilibrium is not reached in the normal cell
which actively extrudes solute and hence water from the cell. Particularly useful in this
regard is the stoichiometry of the Na/K pump that moves 3Na
+
ions out of the cell for
each 2K
+
ions taken up into the cell. With each cycle of the pump, it moves one
osmolyte out of the cell. Since this osmolyte is charged, an intracellular anion follows
the Na
+
out of the cell, and water follows by osmosis. Thus, the maintenance of cell
volume is in part an active transport process that is ATP-dependent. The maintenance of
cell volume is a steady state phenomenon where the passive influx of solute and water is
matched by an active efflux of solute (and hence water)S.
c) Restoring cell volume in hyper-osmotic (hypertonic) media.