14
U N I T 1
Cell and Tissue Function
A host of genetic disorders known as
channelopathies
involve mutations in channel proteins. For example,
in cystic fibrosis (see Chapter 23), the primary defect
resides in an abnormal chloride channel, which results
in increased sodium and water reabsorption that
causes respiratory tract secretions to thicken and
occlude the airways.
Diffusion
Diffusion refers to the passive process by which mol-
ecules and other particles in a solution become widely
dispersed and reach a uniform concentration because of
energy created by their spontaneous kinetic movements.
In the process of reaching a uniform concentration,
these molecules and particles move “downhill” from
an area of higher to an area of lower concentration. If
the molecules or particles carry a net charge, both the
concentration gradient and the electrical potential dif-
ference across the membrane influence transport.
Lipid-soluble molecules, such as oxygen, carbon
dioxide, alcohol, and fatty acids, become dissolved
in the lipid matrix of the cell membrane and diffuse
through the membrane in the same manner that diffu-
sion occurs in water. Other substances diffuse through
minute pores of the cell membrane.
Simple Diffusion.
Simple diffusion means that the
kinetic movement of molecules or ions occurs through
a membrane opening or through intermolecular spaces
without any interaction with a carrier protein. The rate
of diffusion depends on how many particles are avail-
able for diffusion, the kinetic movement of the particles,
and the number and size of the openings in the mem-
brane through which the molecules or ions can move.
Facilitated Diffusion.
Like simple diffusion, facilitated
diffusion occurs down a concentration gradient; thus, it
does not require input of metabolic energy. Unlike simple
diffusion, however, facilitated diffusion requires a trans-
port protein. Some substances, such as glucose, can-
not pass unassisted through the cell membrane because
they are not lipid soluble or they are too large to pass
through the membrane’s pores. These substances com-
bine with special transport proteins at the membrane’s
outer surface, are carried across the membrane attached
to the transporter, and then are released. In facilitated
diffusion, a substance can move only from an area of
higher concentration to one of lower concentration. The
rate at which a substance moves across the membrane
by facilitated diffusion depends on the difference in con-
centration between the two sides of the membrane. Also
important are the availability of transport proteins and
the rapidity with which they can bind and release the
substance being transported. It is thought that insulin,
which facilitates the movement of glucose into cells, acts
by increasing the availability of glucose transporters in
the cell membrane.
Ion Channels and Gates.
Ion channels (leak channels)
are integral proteins that span the width of the membrane
and are normally composed of several polypeptides or
protein subunits that form a gating system (Fig. 1-12).
Specific stimuli cause the protein subunits to undergo
conformational changes to form an open channel or gate
through which the ions can move. In this way, ions do not
need to cross the lipid-soluble portion of the membrane
but can remain in the aqueous solution that fills the ion
channel. Many of the ion channels are highly selective for
transport of one or more specific ions or molecules. This
selectivity results from the characteristics of the channel
itself, such as its diameter, its shape, and the nature of elec-
trical charges and chemical bonds along its inside surface.
The cell membrane contains two basic groups of ion
channels: leakage channels and gated channels. Leakage
channels are open even in the unstimulated state,
whereas gated channels open and close in response to
specific stimuli. Three main types of gated channels
are present in the cell membrane:
voltage-gated chan-
nels
, which have electrically operated channels that
open when the membrane potential changes beyond a
certain point;
ligand-gated channels
, which are chemi-
cally operated and respond to specific receptor-bound
ligands, such as the neurotransmitter acetylcholine; and
mechanically gated channels
, which open or close in
response to such mechanical stimulations as vibrations,
tissue stretching, or pressure.
Movement of Water Across the Cell Membrane.
Water molecules move through adjacent phospholipid
FIGURE 1-11.
Secondary active transport systems.
(A)
Symport or cotransport carries the transported
solute (S) in the same direction as the sodium (Na
+
) ion.
(B)
Antiport or countertransport carries the
solute and Na
+
in the opposite direction.
Extracellular
Intracellular
S Na +
S Na +
A
Symporter
Extracellular
Intracellular
S Na +
S
Na +
B
Antiporter