100
Chapter 4
of the substance across the membrane. Oxygen, carbon diox-
ide, fatty acids, and steroid hormones are examples of nonpo-
lar molecules that diffuse rapidly through the lipid portions
of membranes. Most of the organic molecules that make up
the intermediate stages of the various metabolic pathways
(Chapter 3) are ionized or polar molecules, often containing
an ionized phosphate group, and thus have a low solubility in
the lipid bilayer. Most of these substances are retained within
cells and organelles because they cannot diffuse across the
lipid barrier of membranes.
Diffusion of Ions Through Protein Channels
Ions such as Na
+
, K
+
, Cl
, and Ca
2+
diffuse across plasma
membranes at much faster rates than would be predicted from
their very low solubility in membrane lipids. Moreover, dif-
ferent cells have quite different permeabilities to these ions,
whereas nonpolar substances have similar permeabilities in
different cells. The fact that artifi
cial lipid bilayers containing
no protein are practically impermeable to these ions indicates
that the protein component of the membrane is responsible for
these permeability differences.
As we have seen (Chapter 3), integral membrane pro-
teins can span the lipid bilayer. Some of these proteins form
channels
that allow ions to diffuse across the membrane. A
single protein may have a conformation similar to that of a
doughnut, with the hole in the middle providing the chan-
nel for ion movement. More often, several proteins aggregate,
each forming a subunit of the walls of a channel (
Figure
4–5
). The diameters of protein channels are very small, only
slightly larger than those of the ions that pass through them.
The small size of the channels prevents larger, polar, organic
molecules from entering or leaving.
An important characteristic of ion channels is that they
show a selectivity for the type of ion that can diffuse through
them. This selectivity is based on the channel diameter, the
charged and polar surfaces of the protein subunits that form
the channel walls and electrically attract or repel the ions, and
on the number of water molecules associated with the ions
(so-called waters of hydration). For example, some channels
(K
+
channels) allow only potassium ions to pass, while oth-
ers are specifi c for sodium (Na
+
channels). For this reason,
two membranes that have the same permeability to potassium
because they have the same number of K
+
channels may have
quite different permeabilities to sodium if they contain differ-
ent numbers of Na
+
channels.
Role of Electrical Forces on Ion Movement
Thus far we have described the direction and magnitude of
solute diffusion across a membrane in terms of the solute’s con-
centration difference across the membrane, its solubility in the
membrane lipids, the presence of membrane ion channels, and
the area of the membrane. When describing the diffusion of
ions, since they are charged, one additional factor must be con-
sidered: the presence of electrical forces acting upon the ions.
A separation of electrical charge exists across plasma mem-
branes. This is known as a
membrane potential
(
Figure 4–6
),
the origin of which will be described in Chapter 6 in the con-
text of nerve cell function. The membrane potential provides an
electrical force that infl uences the movement of ions across the
membrane. Electrical charges of the same sign, both positive or
both negative, repel each other, while opposite charges attract.
For example, if the inside of a cell has a net negative charge
with respect to the outside, as is true in most cells, there will
be an electrical force attracting positive ions into the cell and
repelling negative ions. Even if there were no difference in ion
concentration across the membrane, there would still be a net
movement of positive ions into and negative ions out of the cell
because of the membrane potential. Thus, the direction and
magnitude of ion fl
uxes across membranes depend on both
the concentration difference
and
the electrical difference (the
membrane potential). These two driving forces are collectively
known as the
electrochemical gradient
across a membrane.
It is important to recognize that the two forces that
make up the electrochemical gradient may oppose each other.
Thus, the membrane potential may be driving potassium ions,
for example, in one direction across the membrane, while the
concentration difference for potassium is driving these ions in
the opposite direction. The net movement of potassium in this
case would be determined by the relative magnitudes of the
two opposing forces—that is, by the electrochemical gradient
across the membrane.
Regulation of Diffusion Through Ion Channels
Ion channels can exist in an open or closed state (
Figure 4–7
),
and changes in a membrane’s permeability to ions can occur
rapidly as these channels open or close. The process of open-
ing and closing ion channels is known as
channel gating,
like the opening and closing of a gate in a fence. A single ion
channel may open and close many times each second, suggest-
ing that the channel protein fl uctuates between two (or more)
conformations. Over an extended period of time, at any given
electrochemical gradient, the total number of ions that pass
through a channel depends on how often the channel opens
and how long it stays open.
Three factors can alter the channel protein conformations,
producing changes in how long or how often a channel opens.
First, the binding of specifi c molecules to channel proteins may
directly or indirectly produce either an allosteric or covalent
change in the shape of the channel protein. Such channels are
termed
ligand-gated channels,
and the ligands that infl uence
them are often chemical messengers. Second, changes in the
membrane potential can cause movement of the charged regions
on a channel protein, altering its shape—these are
voltage-
gated channels.
Third, physically deforming (stretching) the
membrane may affect the conformation of some channel pro-
teins—these are
mechanically-gated channels.
A particular type of ion may pass through several dif-
ferent types of channels. For example, a membrane may con-
tain ligand-gated K
+
channels, voltage-gated K
+
channels, and
mechanically-gated K
+
channels. Moreover, the same mem-
brane may have several types of voltage-gated K
+
channels,
each responding to a different range of membrane voltage, or
several types of ligand-gated K
+
channels, each responding to
a different chemical messenger. The roles of these gated chan-
nels in cell communication and electrical activity will be dis-
cussed in Chapters 5 through 7.
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