Voltage-Gated Ion Channels and the Action Potential
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Transcript of Voltage-Gated Ion Channels and the Action Potential
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Voltage-Gated Ion Channels and theAction Potential
jdk3
Principles of Neural Science, chaps 8&9
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• The Action Potential– Generation– Conduction
• Voltage-Gated Ion Channels– Diversity – Evolutionary Relationships
Voltage-Gated Ion Channels and theAction Potential
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Electronically Generated Current Counterbalances the Na+ Membrane Current
Command
g = I/V
PNS, Fig 9-2
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Equivalent Circuit of the MembraneConnected to the Voltage Clamp
Im
VC
Imon
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For Large Depolarizations, Both INa and IK Are Activated
PNS, Fig 9-3
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IK is Isolated By Blocking INa
PNS, Fig 9-3
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INa is Isolated By Blocking IK
PNS, Fig 9-3
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Vm = the Value of the Na Battery Plus theVoltage Drop Across gNa
Im
VC
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Calculation of gNa
Vm = ENa + INa/gNa
INa = gNa (Vm - ENa)
gNa = INa/(Vm - ENa)
PNS, Fig 9-3
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gNa and gK Have
Two Similarities and Two Differences
PNS, Fig 9-6
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Voltage-Gated Na+ Channels Have Three States
PNS, Fig 9-9
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Total INa is a Population Phenomenon
PNS, Fig 9-3
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Na+ Channels Open in an All-or-None Fashion
PNS, Fig 9-12
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The Action Potential is Generated bySequential Activation of gNa and gK
PNS, Fig 9-10
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Negative Feedback Cycle Underlies Falling Phase of the Action Potential
Depolarization
Open Na+
Channels
Inward INa
Na+ Inactivation
Increased gK+
Fast
Slow
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Local Circuit Flow of Current Contributes toAction Potential Propagation
PNS, Fig 8-6
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Conduction Velocity Can be Increased by Increased Axon Diameter and by Myelination
Increased Axon Diameter ra I dV/dt
Cm dV/dtMyelination
∆V = ∆Q/C+ + + +
- - - -
+ + + +
- - - -
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Myelin Speeds UpAction Potential Conduction
PNS, Fig 8-8
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• The Action Potential– Generation– Conduction
• Voltage-Gated Ion Channels– Diversity – Evolutionary Relationships
Voltage-Gated Ion Channels and theAction Potential
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Opening of Na+ and K + Channels is Sufficient to Generate the Action Potential
--
----
--
--
--
----+
+
+
+
+
+
+
+
+
+
+
+
--
----
--
--
--
----
+
+
+
+
+
+
+
+
+
+
++
+
Rising Phase Falling Phase
Na + Channels Open Na + Channels Close;K+ Channels Open
Na +
K+
Na +
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However, a Typical Neuron Has Several Types of
Voltage-Gated Ion Channels
--
----
--
--
--
----+
+
+
+
+
+
+
+
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Functional Properties of Voltage-GatedIon Channels Vary Widely
• Selective permeability
• Kinetics of activation
• Voltage range of activation
• Physiological modulators
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Voltage-Gated Ion Channels Differ in theirSelective Permeability Properties
Cation PermeableNa+
K+
Ca++
Na+, Ca++, K+
Anion PermeableCl -
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Functional properties of Voltage-GatedIon Channels Vary Widely
• Selective permeability
• Kinetics of activation
• Voltage range of activation
• Physiological modulators
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V
I
Time
Voltage-Gated K+ Channels Differ Widely in Their Kinetics of Activation and Inactivation
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Functional properties of Voltage-GatedIon Channels Vary Widely
• Selective permeability
• Kinetics of activation
• Voltage range of activation
• Physiological modulators
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Voltage-Gated Ca++ Channels Differ in Their Voltage Ranges of Activation
Pro
babi
lity
of C
hann
el O
peni
ng
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The Inward Rectifier K+ Channels and HCN Channels Are Activated by Hyperpolarization
Pro
babi
lity
of C
hann
el O
peni
ng
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Functional properties of Voltage-GatedIon Channels Vary Widely
• Selective permeability
• Kinetics of activation
• Voltage range of activation
• Physiological modulators: e.g., phosphorylation, binding of intracellular Ca++ or cyclic nucleotides, etc.
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Physiological Modulation
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HCN Channels That Are Opened by Hyperpolarization Are Also Modulated by cAMP
Pro
babi
lity
of C
hann
el O
peni
ng
+cAMP
-120 -90 -60
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Voltage-Gated Ion Channels Belong toTwo Major Gene Superfamilies
I. Cation Permeant
II. Anion Permeant
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Voltage-Gated Ion Channel Gene Superfamilies
I) Channels With Quatrameric Structure Related to Voltage-Gated, Cation-Permeant Channels:
A) Voltage-gated:•K+ permeant•Na+ permeant•Ca++ permeant•Cation non-specific permeant
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Voltage-Gated Ion Channel Gene Superfamily
I) Channels With Quatrameric Structure Related to Voltage-Gated, Cation-Permeant Channels:
A) Voltage-gated:•K+ permeant•Na+ permeant•Ca++ permeant•Cation non-specific permeant (HCN)
Structurally related to-
B) Cyclic Nucleotide-Gated (Cation non-specific permeant)
C) K+-permeant leakage channels
D) TRP Family (cation non-specific); Gated by various stimuli, such as osmolarity, pH, mechanical force, ligand binding and temperature
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The -Subunits of Voltage-Gated ChannelsHave Been Cloned
PNS, Fig 6-9
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Voltage-Gated Cation-Permeant Channels Have
a Basic Common Structural Motif
That is Repeated Four-fold
PNS, Fig 9-14
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Four-Fold Symmetry of Voltage-Gated Channels Arises in Two Ways
I IV
III
I IVII III
x4
K+ Channels, HCN Channels Na+ or Ca++ Channels
II
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Inward Rectifier K+ Channels Have OnlyTwo of the Six Alpha-Helices per Subunit
PNS, Fig 6-12
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Leakage K+ Channels Are Dimers ofSubunits With Two P-Loops Each
PNS, Fig 6-12
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P-Loops Form the Selectivity Filter of Voltage-Gated Cation-Permeant Channels
PNS, Fig 9-15
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Voltage-Gated Ion ChannelGene Superfamilies
II) “CLC” Family of Cl--Permeant Channels (dimeric structure):
Gated by:•Voltage - particularly important in skeletal muscle•Cell Swelling •pH
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Voltage-Gated Cl- Channels Differ in Sequence and Structure from Cation-
Permeant Channels
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Voltage-Gated Cl- Channels are Dimers
x2