Transcript 87881e9f4bc5cca

IONS AND VOLTAGES
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THE POTASSIUM GRADIENT AND THE
RESTING VOLTAGE
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Ions are electrically charged.
This fact has two consequences for
membranes.
First, the movement of ions across a
membrane will tend to change the
voltage across that membrane.
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If positive ions leave the cytosol, they will
leave the cytosol with a negative voltage, and
vice versa.
Second, a voltage across a membrane will
exert a force on all the ions present.
If the cytosol has a negative voltage, then
positive ions such as sodium and potassium
will be attracted in from the extracellular
medium.
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Typical Concentrations for Five Important Ions in
Mammalian Cytosol and Extracellular Medium
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The positively charged potassium ion cannot
cross the lipid bilayer but passes easily through
a water-filled tube in the potassium channel
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GENERAL PROPERTIES OF
CHANNELS
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Channels are integral membrane proteins that
form water-filled tubes through the
membrane.
the gap junction channel (page 55), porin
(page 262), and the potassium channel.
Channels that, like the potassium channel,
are selective for particular ions can set up
transmembrane voltages.
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The gap junction channel is much less
selective than the potassium channel.
It forms a tube, 1.5 nm in diameter, through
which any solute of Mr ≤ 1000 can pass.
The gap junction channel is not always open.
It opens only when it connects with a second
gap junction channel on another cell, forming
a tube through which solutes can pass from
the cytosol of one cell to the cytosol of the
other.
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Channels that are sometimes open and
sometimes shut are said to be gated.
When a gap junction channel contacts
another on another cell, its gate opens and
solute can pass through
at other times the gate is shut.
The usefulness of gating is obvious: if the
gap junction channels not contacting others
were open, many solutes, including ATP and
sodium, would leak out into the extracellular
fluid exhausting the cell’s energy currencies.
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Porin in the outer mitochondrial membrane
plays an important role in energy conversion.
It forms a very large diameter tube that
allows all solutes of Mr ≤ 10,000 to pass and
seems to spend a large fraction of time open
under most circumstances.
This is why the outer mitochondrial
membrane is permeable to most solutes and
ions.
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Cytochrome c —Vital But
Deadly
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the electron carrier cytochrome c
resides in the intermembrane space
between the outer and inner
mitochondrial membranes and helps the
electron transport chain to convert
energy as NADH to energy as the
hydrogen ion electrochemical gradient
across the mitochondrial inner
membrane (page 266).
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Although cytochrome c is a soluble protein of
relative molecular mass 12,270, it cannot
escape from the intermembrane space into
the cytosol because porin, the channel of the
outer mitochondrial membrane, only allows
solutes of Mr ≤ 10,000 to pass.
Although cytochrome c is essential for
mitochondrial function, it has another, deadly
role.
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If cytochrome c comes into contact with a
class of cytosolic enzymes called caspases, it
activates them, turning on the process of cell
suicide called apoptosis (page 417).
Under certain conditions, porin can associate
with other proteins to form a channel of
larger diameter; when this happens,
cytochrome c can leak out and the cell dies
by apoptosis.
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This process seems to occur in hearts
during heart attacks, and in the brain
during a stroke: there is therefore a
considerable research effort aimed at
preventing this from occurring.
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Poisoned Hearts Are
Stronger
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Digitalis is used to treat heart failure.
Digitalis inhibits the sodium/potassium
ATPase and is extremely toxic.
Nevertheless, a small dose, which inhibits the
sodium/potassium pump just a little, causes
the heart muscle to beat more strongly.
The reason is that inhibiting the
sodium/potassium pump just a little causes a
small increase of cytosolic sodium
concentration.
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Because the sodium/calcium exchanger has
three binding sites for sodium, its activity is
extremely sensitive to sodium concentration,
and even a small increase of cytosolic sodium
reduces its activity significantly.
The calcium concentration in the cytosol
therefore rises.
The mechanical motor that drives heart
contraction (Chapter 18) is controlled by
calcium, so that a small increase of cytosolic
calcium makes the heart beat more strongly.
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All the cells of our bodies have one of these two
calcium pumps—the sodium/calcium exchanger or
the calcium ATPase—and many have both.
Because of the action of these carriers, the calcium
concentration in the cytosol is much less than the
concentration in the extracellular medium: usually
about 100 nmol liter−1 compared with 1 mmol
liter−1.
Because the resting voltage is attracting the
positively charged calcium ions inward, the overall
result is a large electrochemical gradient favoring
calcium entry into cells.
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Measuring the
Transmembrane Voltage
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In 1949 Gilbert Ling and Ralph Gerard
discovered that when a fine glass
micropipette filled with an electrically
conducting solution impaled a cell, the
plasma membrane sealed to the glass,
so that the transmembrane voltage was
not discharged.
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The voltage difference between a wire
inserted into the micropipette and an
electrode in the extracellular fluid could
then be measured.
By passing current through the
micropipette, the transmembrane
voltage could be altered.
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Twenty-five years later Erwin Neher and Bert
Sakmann showed that the micropipette did
not have to impale the cell.
If it just touched the cell, a slight suction
caused the plasma membrane to seal to the
glass.
The technique, called cell-attached patch
clamping, can measure currents through the
few channels present in the tiny patch of
membrane within the pipette.
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Stronger suction bursts the membrane within
the pipette.
The transmembrane voltage can now be
measured.
Alternatively, current can be passed through
the micropipette to change the
transmembrane voltage—this is the whole
cell patch clamp technique.
In 1991, Neher and Sakmann received the
Nobel prize for medicine.
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Action of the calcium ATPase.
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