the cell has been stimulated. At the neuromuscular junction of vertebrates, motor nerve
terminals, when they are invaded by an action potential, release a neurotransmitter, acetylcholine (ACh), which diffuses through the synaptic cleft to the muscle postsynaptic membrane, where it is recognized by a transmembrane (TM) receptor, the nicotinic ACh receptor
(nAChR), which opens a relatively non-specific cation-selective channel (see § 1.6.2). The
net entry into the cytosol of the muscle fiber of positive charges, principally carried by Na
+
ions, lowers the membrane potential of its plasma membrane to the level needed to activate
the voltage-sensitive sodium channel and trigger an action potential, which propagates along
its length. This in turn causes the release in the cytosol of calcium ions stored in the lumen of
an internal compartment, the sarcoplasmic reticulum (SR), setting off muscle contraction.
In tissues such as the liver or the eye lens, the cytosols of neighboring cells are put into
communication one with another by TM channels, the connexons, which assemble laterally in
the membrane plane into gap junctions. As a safety device, an abnormal increase of the
cytosolic concentration of calcium in a cell, as happens if the integrity of its membrane is
compromised, causes the connexons to close, disconnecting the affected cell from the rest of
the tissue. Channels can also be activated mechanically. Such is the case of mechanosensitive
channels, which, in bacteria, open in response to osmotic pressure changes that tend to expand
the plasma membrane, thus releasing the pressure, or, in eukaryotes, play important roles in
physiological processes such as touch, pain, or hearing.
• In the examples we have seen thus far, existing gradients are dissipated. They must be
recreated, which is the role of pumps that tap various sources of energy. ATP is hydrolyzed
to ADP and inorganic phosphate by pumps such as the plasma membrane Na
+
,K
+
-ATPase,
which sets up the transmembrane Na
+ and K
+ gradients, or the Ca
2+ -ATPase, which pumps
back Ca
2+ ions into the SR lumen so as to end muscle contraction (see § 1.6.3). ATP is also
hydrolyzed to operate the multidrug resistance pumps that extrude toxic compounds, such
as antibiotics or anticancer drugs. ATP is regenerated from ADP and phosphate by the
F 1 F O -ATP synthase, at the expense of dissipating a transmembrane proton electrochemical
gradient. The free energy stored in the gradient is first converted, at the level of the TM
complex F O , into mechanical energy, which the F 1 domain, which lies in either the cytosol or
the mitochondrial or chloroplastic matrix, converts into chemical energy by forcing the
phosphorylation of ADP into ATP. In mitochondria, the proton gradient is created, in the
course of respiration, by a series of membrane complexes that oxidize reducing molecules by
transferring their electrons to O 2 , releasing H 2 O, and consuming and pumping protons in the
process. In chloroplasts, the proton gradient is the result of oxygen-evolving photosynthesis, a
process, also catalyzed by several TM complexes, in which the energy of photons is exploited
to extract electrons and H
+ ions from water, releasing gaseous O 2 and reduced electron
carriers. In some archaebacteria, a proton gradient is created, without involving any redox
chemistry, by a single, small TM protein, bacteriorhodopsin (BR), which uses the lightinduced isomerization of its cofactor, retinal, as a source of mechanical energy that sets off a
series of transconformations whose end result is to extrude protons from the cytosol through
the plasma membrane (see § 1.6.1).
10
1 Membrane Proteins and Their Natural Environment
terminals, when they are invaded by an action potential, release a neurotransmitter, acetylcholine (ACh), which diffuses through the synaptic cleft to the muscle postsynaptic membrane, where it is recognized by a transmembrane (TM) receptor, the nicotinic ACh receptor
(nAChR), which opens a relatively non-specific cation-selective channel (see § 1.6.2). The
net entry into the cytosol of the muscle fiber of positive charges, principally carried by Na
+
ions, lowers the membrane potential of its plasma membrane to the level needed to activate
the voltage-sensitive sodium channel and trigger an action potential, which propagates along
its length. This in turn causes the release in the cytosol of calcium ions stored in the lumen of
an internal compartment, the sarcoplasmic reticulum (SR), setting off muscle contraction.
In tissues such as the liver or the eye lens, the cytosols of neighboring cells are put into
communication one with another by TM channels, the connexons, which assemble laterally in
the membrane plane into gap junctions. As a safety device, an abnormal increase of the
cytosolic concentration of calcium in a cell, as happens if the integrity of its membrane is
compromised, causes the connexons to close, disconnecting the affected cell from the rest of
the tissue. Channels can also be activated mechanically. Such is the case of mechanosensitive
channels, which, in bacteria, open in response to osmotic pressure changes that tend to expand
the plasma membrane, thus releasing the pressure, or, in eukaryotes, play important roles in
physiological processes such as touch, pain, or hearing.
• In the examples we have seen thus far, existing gradients are dissipated. They must be
recreated, which is the role of pumps that tap various sources of energy. ATP is hydrolyzed
to ADP and inorganic phosphate by pumps such as the plasma membrane Na
+
,K
+
-ATPase,
which sets up the transmembrane Na
+ and K
+ gradients, or the Ca
2+ -ATPase, which pumps
back Ca
2+ ions into the SR lumen so as to end muscle contraction (see § 1.6.3). ATP is also
hydrolyzed to operate the multidrug resistance pumps that extrude toxic compounds, such
as antibiotics or anticancer drugs. ATP is regenerated from ADP and phosphate by the
F 1 F O -ATP synthase, at the expense of dissipating a transmembrane proton electrochemical
gradient. The free energy stored in the gradient is first converted, at the level of the TM
complex F O , into mechanical energy, which the F 1 domain, which lies in either the cytosol or
the mitochondrial or chloroplastic matrix, converts into chemical energy by forcing the
phosphorylation of ADP into ATP. In mitochondria, the proton gradient is created, in the
course of respiration, by a series of membrane complexes that oxidize reducing molecules by
transferring their electrons to O 2 , releasing H 2 O, and consuming and pumping protons in the
process. In chloroplasts, the proton gradient is the result of oxygen-evolving photosynthesis, a
process, also catalyzed by several TM complexes, in which the energy of photons is exploited
to extract electrons and H
+ ions from water, releasing gaseous O 2 and reduced electron
carriers. In some archaebacteria, a proton gradient is created, without involving any redox
chemistry, by a single, small TM protein, bacteriorhodopsin (BR), which uses the lightinduced isomerization of its cofactor, retinal, as a source of mechanical energy that sets off a
series of transconformations whose end result is to extrude protons from the cytosol through
the plasma membrane (see § 1.6.1).
10
1 Membrane Proteins and Their Natural Environment