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Biology 463 - Neurobiology
Topic 3
The Neuronal Membrane
at Rest
Lange
Introduction
Resting Potential – the chemical makeup of the neuron when it is at “rest”….
meaning there is no message present
Action Potential – the chemical makeup of the neuron when it is “active”….
meaning there is a message present
Please note that the image above displays neurons in a way that can perpetuate
a misconception: The Action Potential does NOT occur throughout the entire
neuron instantly, but instead… the Action Potential will exist in a small portion of
the neuron and will travel along the length of the neuron.
The Cast of Chemicals Involved the Generation of an
Action Potential
•
Cytosolic and Extracellular Fluids
– water is a polar solvent
– Various cations (+) and anions (-)
• The Phospholipid Membrane
– Hydrophilic (Polar) Head
• Materials that dissolve in water will pass through
– Hydrophobic (Nonpolar) Tails
• Materials that dissolve in water will NOT pass through
• Materials that dissolve in non-polar solvents (such as oils)
will pass through
– The phospholipids will aggregate in a water
media to create what is known as the
Phospholipid Bilayer
With the phospholipid molecule having
the polar head region and the nonpolar
tail region, when the phospholipid bilayer
(PLB) is formed, the property that is seen
is a PLB that serves as a selectively
permeable membrane… a crucial feature
for message transport both in the
“electrical message” and the chemical
message aspect of the neuron.
•
Proteins
– Molecules
• Enzymes
• Cytoskeletal elements
• Receptors
• Specialized transmembrane proteins
– Control resting and action potentials
It is estimated that
there can be
hundreds of billions
of different types of
proteins that can be
made, and our best
estimate is that there
are roughly 100,000
different proteins
produced and used
in the human body.
•
Protein structure is
enormously diverse:
• The 20 different
amino acids
consisting of an
alpha carbon, a
carboxyl group,
hydrogen, and
some sort of R
(residue) group
• Diversity is due
to the variation
in the R group
In the neuron, proteins are synthesized by ribosomes in two primary areas:
– Neuronal cell body (soma)
– Axon terminals
In both places, the ribosomes assemble amino acids into polypeptide chains
(connected by polypeptides)
Levels of protein structure.
Amino acid
Amino acid
Amino acid
Amino acid
Amino acid
(a) Primary structure:
The sequence of
amino acids forms the
polypeptide chain.
(b) Secondary structure:
The primary chain forms
spirals (-helices) and
sheets (-sheets).
-Helix: The primary chain is coiled
to form a spiral structure, which is
stabilized by hydrogen bonds.
-Sheet: The primary chain “zig-zags” back
and forth forming a “pleated” sheet. Adjacent
strands are held together by hydrogen bonds.
(c) Tertiary structure:
Superimposed on secondary structure.
-Helices and/or -sheets are folded up
to form a compact globular molecule
held together by intramolecular bonds.
(d) Quaternary structure:
Two or more polypeptide chains, each
with its own tertiary structure, combine
to form a functional protein.
Tertiary structure of prealbumin
(transthyretin), a protein that
transports the thyroid hormone
thyroxine in serum and cerebrospinal fluid.
Quaternary structure of a
functional prealbumin molecule.
Two identical prealbumin subunits
join head to tail to form the dimer.
Amino acid
Amino acid
Amino acid
Amino acid
Amino acid
(a) Primary structure:
The sequence of amino acids forms the polypeptide chain.
-Helix: The primary chain is coiled
to form a spiral structure, which is
stabilized by hydrogen bonds.
-Sheet: The primary chain “zig-zags” back
and forth forming a “pleated” sheet. Adjacent
strands are held together by hydrogen bonds.
(b) Secondary structure:
The primary chain forms spirals (-helices) and sheets (-sheets).
Tertiary structure of prealbumin
(transthyretin), a protein that
transports the thyroid hormone
thyroxine in serum and cerebrospinal fluid.
(c) Tertiary structure:
Superimposed on secondary structure. -Helices and/or -sheets are
folded up to form a compact globular molecule held together by
intramolecular bonds.
Levels of protein structure.
Quaternary structure of
a functional prealbumin
molecule. Two identical
prealbumin subunits
join head to tail to form
the dimer.
(d) Quaternary structure:
Two or more polypeptide chains, each with its own tertiary structure,
combine to form a functional protein.
An example of the progression in complexity of structure in proteins with the final
quaternary structure being that of hemoglobin.
Proteins develop in a variety of
forms in neurons to form
– Ion channels using channel
proteins
– Ion pumps using other
proteins
The Movement of Ions
•
Simple diffusion is an option for
small ions and other small
molecules
Electricity and Circuits
• Electrical current influences ion
movement
• Electrical conductance (g) and
resistance (R);
R = 1/g
• Electrical potential (voltage)
Chemicals Involved in the Conduction of Electricity
•
Electricity
– Electrical current can flow across a membrane
– Ohm’s law
I = gV
(current = conductance x electrical potential)
The Ionic Basis of The Resting Membrane Potential
•
Membrane potential:
Voltage across the
neuronal membrane
• Equilibrium Potential
(Eion)
– No net movement of ions
when separated by a
phospholipid membrane
– Equilibrium reached when
K+ channels inserted into
the phospholipid bilayer
– Electrical potential
difference that exactly
balances ionic
concentration gradient
• Equilibrium Potential
Voltmeter
Plasma
membrane
Ground electrode
outside cell
Microelectrode
inside cell
Axon
Neuron
Depolarizing stimulus
Hyperpolarizing stimulus
+50
Inside
positive
0
Inside
negative
Depolarization
–50
–70
Resting
potential
–100
0
1
2
3
4
5
6
Membrane potential (voltage, mV)
Membrane potential (voltage, mV)
+50
7
–50
Resting
potential
–70
Hyperpolarization
–100
0
Time (ms)
(a)
0
1
2
3
4
Time (ms)
(b)
5
6
7
Depolarized region
Stimulus
Plasma
membrane
(a) Depolarization
(b) Spread of depolarization
Membrane potential (mV)
Active area
(site of initial
depolarization)
–70
Resting potential
Distance (a few mm)
Outside
cell
Na+
Inside
cell
Inside
K+
cell
3 Repolarizing phase: Na+
channels inactivating, K+
channels open
Membrane potential (mV)
K+
2 Depolarizing phase: Na+
channels open
Action potential
+30
3
0
2
PNa
PK
–55
–70
1
0
4
1
Outside cell Sodium Potassium
channel channel
Na+
Activation
K+
gates
Inactivation gate
1 Resting state: All gated Na+
and K+ channels closed
(Na+ activation gates closed;
inactivation gates open)
Inside
cell
Copyright © 2010 Pearson Education, Inc.
Na+
Threshold
1
2
3
Time (ms)
Relative membrane
permeability
Outside
cell
4
Outside
cell
Na+
Inside
cell
4 Hyperpolarization: K+
channels remain open;
Na+ channels resetting
K+
Membrane potential (mV))
Voltage
at 2 ms
+30
Voltage
at 0 ms
Voltage
at 4 ms
–70
(a) Time = 0 ms
Resting potential
Peak of action potential
Hyperpolarization
(b) Time = 2 ms
(c) Time = 4 ms
Membrane potential (mV)
Voltage
Action
potentials
+30
–70
Threshold
Stimulus
amplitude
0
Time (ms)
Absolute refractory
period
Membrane potential (mV)
+30
Relative refractory
period
Depolarization
(Na+ enters)
0
Repolarization
(K+ leaves)
After-hyperpolarization
–70
Stimulus
0
1
2
Time (ms)
3
4
5
• Equilibrium Potentials (Cont’d)
– The Nernst Equation
• Calculates the exact value of the equilibrium potential for each ion
in mV
• Takes into consideration:
– Charge of the ion
– Temperature
– Ratio of the external and internal ion concentrations
•
The Distribution of Ions Across
The Membrane
•
The sodium-potassium pump
– Enzyme - breaks down ATP when Na present
– Calcium pump: Actively transports Ca2+ out of
cytosol
Cell interior
Na+
15 mM
Cell
exterior
Na+
+
Na+ Na
K+
Na+–K+
pump
150 mM
Cl–
10 mM
Na+
Na+
A–
Na+
100 mM
150 mM
A–
0.2 mM
Cell exterior
K+
5 mM
K+
Cl–
120 mM
Cell
interior
Plasma
membrane
Na+
K+
K+
K+
Seymour Benzer – research leader in studies of Shaker Flies. In the
1970s, his lab was able to associate this mutant’s behavior to a gene
that affects potassium channel development.
Shaker Potassium Channels
Genetic approaches include screening for behavioral changes in animals with
mutations in K+ channel genes. Such genetic methods allowed the genetic
identification of the "Shaker" K+ channel gene in Drosophila before ion
channel gene sequences were well known.
The Shaker (Sh) gene, when mutated, causes a variety of atypical behaviors
in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s
legs will shake (hence the name); even when the fly is unanaesthetized, it
will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan
than regular flies; in their larvae, the repetitive firing of action potentials as
well as prolonged exposure to neurotransmitters at neuromuscular
junctions occurs.
The Sh gene plays a part in the operation of potassium ion channels, which
are integral membrane proteins and are essential to the correct functioning
of the cell.
• Relative Ion Permeabilities of
the Membrane at Rest
– K+ channels: 4 subunits
– Channel selectively permeable to K+
ions
– MacKinnon—2003 Nobel Prize
• Mutations of specific K+ channels;
Inherited neurological disorders
END.