chem 452 - lecture 9 pumps and channels part 2 · 2012. 12. 4. · chem 452, lecture 9 - pumps and...
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Chem 452 - Lecture 9Pumps and Channels
Part 2Question of the Day: How is the action potential of nerve conduction like a human wave at a Packer game?
Chem 452, Lecture 9 - Pumps and Channels
ATPase Pumps!✦ The energetics of active transport
• Na+/K+ ATPase‣ Pumps 3 Na+ out while pumping 2 K+ in.
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14 mM143 mM
157 mM 4 mM
(-)
(+)-50 mV
3
2
-50 kJ/mol
Chem 452, Lecture 9 - Pumps and Channels
✦ The energetics of active transport• Na+/K+ ATPase
‣ Pumps 3 Na+ out while pumping 2 K+ in.
ATPase Pumps!
3
ΔG = RT ln c2c1
⎛⎝⎜
⎞⎠⎟+ ZFΔV
= 8.314 x 10−3 kJmol•K
⎛⎝⎜
⎞⎠⎟
310 K( ) ln 0.143( )3 0.157( )2
0.014( )3 0.004( )2⎛
⎝⎜⎞
⎠⎟+ +1( ) 96.5 kJ
mol•V⎛⎝⎜
⎞⎠⎟+0.050V( )
= 36.9 kJmol
+ 4.8 kJmol
= 41.7 kJmol
Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Due to a small movement of K+ ions, the resting
nerve fiber has a resting membrane potential of -60mV
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ When a nerve fires, the membrane potential
inverts in a wave that move along the axon of the nerve fiber.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ When a nerve fires, the membrane potential
inverts in a wave that move along the axon of the nerve fiber.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The action potential is due to the sequential
opening of a Na+ and a K+ channel.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Channels can be studied using the patch-clamp
technique.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The Na+ channel was the first to be isolated
and structurally characterized.
• 260 kDa chain• 4 internal repeats• Hydrophobicity profiles indicates 5 hydrophobic
rageions (S1, S2, S3, S5, S6)• S4 is highly positively charged
‣ Proposed these acted as voltage sensors.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The K+ channel was more difficult to isolate and
structurally characterize.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The basic channel is illustrated by bacterial K+
channel.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ K+ channel illustrates ion selectivity.
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K+ must give up waters of hydration to pass through the narrow opening in the channel.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ K+ channel illustrates ion selectivity.
• The sequence Thr-Val-Gly-Tyr-Gly is highly conserved.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ K+ channel illustrates ion selectivity.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ K+ channel illustrates ion selectivity.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ K+ channel illustrates basis for rapid transport.
• Charge repulsion increases the rate of flow
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The voltage-gated K+ channel of nerve cells.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The voltage-gated K+ channel of nerve cells.
• Voltage rise opens channel
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Transport is abruptly halted by a plug
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Transport is abruptly halted by a plug
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Neurotransmitters from neighboring nerve cells
trigger the action potential.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Neurotransmitters from neighboring nerve cells
trigger the action potential.
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Acetylcholine is an example of a neurotransmitter
Chem 452, Lecture 4 - Enzymes
Enzyme Inhibition✦ Irreversible Inhibition
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DIPF is related to the poison Sarin gas
Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Acetylcholine triggers a ligand-gated channel.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The Acetylcholine receptor can be isolated with
affinity chromatography using cobratoxin as the ligand.
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Affinity Chromatography
Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The binding of acetylcholine to the he
acetylcholine opens the flow to Na+ and K+ ions.
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The resting, equilibrium potential is -60mV.
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ΔG = RT lnX[ ]inX[ ]out
⎛
⎝⎜⎞
⎠⎟ + zFV
At equilibrium, ΔG = 0
Veq = −RTzF
lnX[ ]inX[ ]out
⎛
⎝⎜⎞
⎠⎟
For Na+ , Veq = + 62 mV
For K+ , Veq = - 98 mV
14 mM143 mM
157 mM 4 mM
(-)
(+)
-50 mV
3
2
-50 kJ/mol
Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The binding of acetylcholine to the he
acetylcholine opens the flow to Na+ and K+ ions.• When the voltage climbs past -40 mV, the voltage-
gated channels are triggered
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ The binding of acetylcholine to the he
acetylcholine opens the flow to Na+ and K+ ions.• When the voltage climbs past -40 mV, the voltage-
gated channels are triggered
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!
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Chem 452, Lecture 9 - Pumps and Channels
Channels and the Action Potential!✦ Transport is abruptly halted by a plug
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Chem 452, Lecture 9 - Pumps and Channels
Next up✦ Lecture 10, Signal Transduction and Sensory
Systems. (Chapter 14 & 33)
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