Sodium Potassium Pump and Nerve Impulse

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Transcript Sodium Potassium Pump and Nerve Impulse

How it works….step by step:
• At rest, the inside of
the neuron is slightly
negative due to a
higher concentration
of positively charged
sodium ions outside
the neuron.
• When stimulated past threshold, sodium
channels open and sodium rushes into the
axon, causing a region of positive charge
within the axon.
• The region of positive charge causes nearby
sodium channels to open. Just after the
sodium channels close, the potassium
channels open wide, and potassium exits the
axon.
• This process continues as a chain-reaction along
the axon. The influx of sodium depolarizes the
axon, and the overflow of potassium repolarizes
the axon.
• The sodium/potassium pump restores the
resting concentrations of sodium and
potassium ions
The Pump In Action
Action Potential
+
Na /
+
K
- ATPase
+
Na /
+
K
Facts
The Na+-K+-ATPase is a highly-conserved integral membrane
protein that is expressed in virtually all cells of higher organisms.
As one measure of their importance, it has been estimated that
roughly 25% of all cytoplasmic ATP is hydrolyzed by sodium
pumps in resting humans. In nerve cells, approximately 70% of
the ATP is consumed to fuel sodium pumps.
Physiologic and Pathologic Significance
The ionic transport conducted by
sodium pumps creates both an
electrical and chemical gradient across
the plasma membrane. This is critical
not only for that cell but, in many cases,
for directional fluid and electrolyte
movement across epithelial sheets.
Some key examples include:
•The cell's resting membrane potential is a
manifestation of the electrical gradient, and the gradient
is the basis for excitability in nerve and muscle cells.
•Export of sodium from the cell provides the driving
force for several facilitated transporters, which
import glucose, amino acids and other nutrients into the
cell.
•Translocation of sodium from one side of an epithelium
to the other side creates an osmostic gradient that drives
absorption of water. Important instances of this
phenomenon can be found in the absorption of water
from the lumen of the small intestine and in the kidney.
Depending on cell type, there are
between 800,000 and 30 million
pumps on the surface of cells. They
may be distributed fairly evenly, or
clustered in certain membrane
domains, as in the basolateral
membranes of polarized epithelial
cells in the kidney and intestine.
Abnormalities in the number or function of Na+K+-ATPases are thought to be involved in
several pathologic states, particular heart
disease and hypertension.
Well-studied examples of this linkage include:
•Excessive renal reabsorption of sodium due to
oversecretion of aldosterone has been associated
with hypertension in humans.
•Several types of heart failure are associated with
significant reductions in myocardial concentration
of Na+-K+-ATPase.
Cation transport occurs in a cycle of changes triggered by
phosphorylation of the pump.
As currently understood, the sequence of events can be
summarized as follows:
•The pump, with bound ATP, binds 3 intracellular Na+ ions.
•ATP is hydrolyzed, leading to phosphorylation of a
cytoplasmic loop of the pump and release of ADP.
•A conformational change in the pump exposes the Na+ ions to
the outside, where they are released.
•The pump binds 2 extracellular K+ ions, leading to
dephosphorylation.
•ATP binds and the pump reorients to release K+ ions inside the
cell.
The pump is ready to go again.
Major hormonal controls over pump activity can be summarized
as follows:
•Thyroid hormones appear to be a major player in
maintaining steady-state concentrations of pumps in
most tissues. This effect appears to result from
stimulation of subunit gene transcription.
•Aldosterone is a steroid hormone with major effects on
sodium homeostasis. It stimulates both rapid and
sustained increases in pump numbers within several
tissues. The sustained effect is due to enhanced
transcription of the genes for both subunits.
Catecholamines have varied effects, depending on the
specific hormone and tissue. For example, dopamine
inhibits Na+-K+-ATPase activity in kidney, while
epinephrine stimulates pump activity in skeletal muscle.
These effects seem to be mediated via phosphorylation or
dephosphorylation of the pumps.
Insulin is a major regulator of potassium homeostasis and
has multiple effects on sodium pump activity. Within
minutes of elevated insulin secretion, pumps have
increased affinity for sodium and increased turnover rate.
Sustained elevations in insulin causes upregulation. In
skeletal muscle, insulin may also recruit pumps stored in
the cytoplasm or activate latent pumps already present in
the membrane.