16
U N I T 1
Cell and Tissue Function
a
phagosome
. The process of pinocytosis, which means
“cell drinking,” is important in the transport of pro-
teins and strong solutions of electrolytes. Phagocytosis,
which means “cell eating,” involves the engulfment and
subsequent killing or degradation of microorganisms
and other particulate matter. Certain cells, such as mac-
rophages and neutrophils, are adept at engulfing and
disposing of invading organisms, damaged cells, and
unneeded extracellular constituents.
Exocytosis
is the mechanism for the secretion of
intracellular substances into the extracellular spaces. It
may be considered a reverse of endocytosis in that the
membrane of the secretory granule fuses with the cell
membrane and allows the contents of the granule to be
released into the extracellular fluid. Exocytosis is impor-
tant in removing cellular debris and releasing substances,
such as hormones and cytokines, synthesized in the cell.
Receptor-mediated endocytosis
involves the binding
of substances to a receptor on the cell surface. Many
of these receptor proteins are concentrated in
clathrin-
coated pits
, which are specific areas of the cell where the
membrane is lined on its cytoplasmic side by a periph-
eral protein called
clathrin
. The interaction between
the proteins in the receptor–ligand complex causes the
membrane to invaginate. The edges of the membrane
around the clathrin-coated pit then fuse, and a por-
tion of the membrane pinches off as an endocytic ves-
icle. Almost immediately after it is formed, the vesicle
loses its clathrin coat and becomes fused with an early
endosome in a manner similar to that involved in non–
receptor-mediated endocytosis. The uptake of choles-
terol transported in the blood as low-density lipoprotein
(LDL) relies on receptor-mediated removal associated
with clathrin-coated pits. This pathway for cholesterol
removal is disrupted in persons who inherit defective
genes for encoding LDL receptors (see Chapter 18).
In addition to clathrin-coated pits and vesicles, there
are a number of othermechanisms bywhich cells can form
endocytotic vesicles. One of these pathways involves the
formation of small invaginations or “little cavities” in
the cell membrane, called
caveolae
, that extend inward,
indenting the cell membrane and the cytoplasm. These
cavities may pinch off and form free vesicles within
the cytoplasm. Caveolae are considered to be sites for
uptake of material into the cell, for expulsion of material
from the cell, and for addition or removal of cell mem-
brane components. In smooth muscle, caveolae project
into the cytoplasm and, analogous to the T tubules in
striated muscle, play an important role in regulating
intracellular calcium concentration and smooth muscle
tone. In addition to transport, caveolae are involved in
a number of other functions such as signal transduction
and may be involved in the pathogenesis of a number of
diseases, including muscular dystrophy.
Generation of Membrane Potentials
Living organisms have electrical properties in which
current flow involves the movement of ions in water.
Electrical potentials exist across the membranes of most
cells in the body. Because these potentials occur at the
level of the cell membrane, they are called
membrane
potentials
. In excitable tissues, such as nerve or muscle
cells, changes in the membrane potential are necessary
for generation and conduction of nerve impulses and
muscle contraction. In other types of cells, such as glan-
dular cells, changes in the membrane potential contrib-
ute to hormone secretion and other functions.
Electrical potentials describe the ability of separated
electrical charges of opposite polarity (+ and −) to do
work. In regard to cells, the oppositely charged particles
are ions, and the barrier that separates them is the cell
membrane. Electrical potentials are measured in volts
(V) or units of electromotive force (EMF). Voltage is
always measured with respect to two points in a system.
For example, the voltage in a car battery (6 or 12 V)
is the potential difference between the two battery ter-
minals. In a cell it is the potential difference between
the inside and outside of the cell membrane. Because
the total amount of charge that can be separated by a
biologic membrane is small, the potential differences are
small and are therefore measured in millivolts (mV), or
1/1000 of a volt.
There are two main factors that alter membrane
potentials: the difference in the concentration of ions on
the inside and outside of the membrane and the perme-
ability of the membrane to these ions. Extracellular and
intracellular fluids are electrolyte solutions containing
approximately 150 to 160 mmol/L of positively charged
ions and an equal concentration of negatively charged
ions. The diffusion of these current-carrying ions is
responsible for generating and conducting membrane
potentials. A
diffusion potential
describes the voltage
generated by ions that diffuse across the cell membrane.
An
equilibrium potential
is one in which there is no
net movement of a particular ion across a membrane
because the diffusion potential and electrical forces gen-
erated by the movement of the ion are exactly balanced.
The magnitude of the equilibrium potential, also known
as the
Nernst potential
, is determined by the ratio of the
concentration of a specific ion on the two sides of the
membrane. The greater the ratio, the greater the ten-
dency for the ion to diffuse in one direction, and there-
fore the greater the electrical forces required to prevent
further diffusion. The Nernst equation (described in the
figure on Understanding Membrane Potentials) can be
used to calculate the equilibrium potential for any uni-
valent ion at a given concentration difference, assum-
ing that membrane is permeable to the ion. When using
the equation, it is generally assumed that the electrical
potential of the extracellular fluid outside the membrane
remains at zero and the potential being calculated is
the electrical potential inside the membrane. It is also
assumed that the sign of the potential is negative (−) if
a positively charged ion diffuses from the inside to the
outside of the membrane and positive (+) if a positively
charged ion diffuses from the outside to the inside of the
membrane.
The
resting membrane potential
represents the period
of time when excitable cells, such as nerve fibers, are not
transmitting signals. Because resting cell membranes are
