Unit 1.Lec 3-The Action Potential: Initiation & Propagation Flashcards
Define Action Potential
Rapid, transient change in membrance potential (Vm)
Explain Na+ channel activation
Responsible for transient inward current that depolarizes membrane
Explain K+ channel activation
Delayed activation responsible for delayed outward current that repolarizes the membrane
Define Threshold Potential
Minimum depolarization required for an action potential to fire
Define Local Current Flow
Action potential propagation along un-myelinated axon
Define Saltatory Conduction
Action potential propagation along myelinated axons. Much faster conduction
Explain AP Refractory Period
Time lag between action potentials
Define Multiple Sclerosis
Degeneration of the myelin sheaths slows conduction
Where are action potential ususally initiated?
Axon hillock
Pathway of an Action Potential
Begins @ resting membrane potential (=-70 mV)–>rapid increase from (-) Vm to (+) called depolarization–>then drops back down to resting Vm: repolarization–>goes beyond resting Vm to stop AP firing: hyperpolarization
How is action potential propagated down the axon?
By voltage-gated ion channels
Describe the Action Potential Threshold
- All-or-none phenomenon
- Minimum depolarization needed to fire AP
What will occur if Vm does not reach threshold
AP will NOT fire
What are some sodium channel blockers?
- TTX
- Riluzole (aka Rilutek)
What is used to estimated membrane potential?
The Goldman Equation
What are 2 mechanisms that will cause Em (Vm) to change?
- By changing internal/external ionic concentrations. (Note: [K+] typically has greatest permeability and influence on Vm)
- By changing the relative permeability of the ions across the plasma membrane
How are ionic permeabilities changed?
By
1. Ligand- gated (e.g. GABA, Glu, 5HT)
2. Voltage-gated (e.g. Na+, K+)
3. Nucleotide-gated (cAMP, cGMP)
4. Inward retifier “leak” channels
5. Mechanosensitive-gated (stretch)
What are voltage-gated ion channels? List the types
“Voltage sensors” with ion selectivity
1. Na+ channel
2. Ca2+ channel
3. K+ channel
4. Cl- channel
5. H+ channel
Structure of the K+ channel
Tetramer (4 subunits)
What part of Na+ and K+ channel senses the change in voltage?
S4 segment, undergoes conformational changes
What are the 3 Conformational States of the voltage-gated Na+ channels?
- Open (“a” or “m” gate)
- Inactived (“l” or “h” gate)
- Closed
What does inactivation of the Na+ channels lead to?
Stops the flow of ions into the cell and leads to repolarization
What state is the Na+ channel when its polarized
Closed
What state is the Na+ channel when its depolarized?
Open—>Inactivated
What state is Na+ channel when its hyperpolarized?
Closed
What does depolarization trigger?
The opening of voltage-gated K+ channels
K+ channels produces the delayes outward current
What occurs when the volated gated K+ channels are opened?
K+ ions rush OUT OF the cell
What does transient efflux (high Pk) leads to?
Hyperpolarization
What is the state of K+ channels during hyperpolarization?
Closed
Hyperpolarization is a built in defense against what?
Hyperexcitability; negative feedback decreases probability of activing more channels
Explain the Na+ and K+ channel Synchrony?
- (Fast Positive Cycle) Rapid activation of Na+ channels causes depolarization
- Na+ channels inactivation STOPS depolarization
- (Slow Negative Cycle) Slower activation of K+ channels contributes to repolarization and eventual hyperpolarization
Explain Action Potential Propagation
- Propagation=movement down the axon
- Action Potential Threshold is the minium depolarization needed to fire an AP
- AP will not fire if Vm is under threshold. AP is an all-or-none phenomenon
Example of Na+ channel blockers
- TTX
- Riluzole (aka Rilutek)
Explain Non-Propagated Depolarization
- If the min. depolarization to reach threshold is not met, the AP will not propagate. Instead, it would spread passively through local current flow (aka remian stagnant)
Non-propagated depolarization spreads passively through local current flow (“Electrotonic Conduction”)
List the 4 key concepts of AP Propagation
- Depolarization attenuates (slowly decreases) as it moves down the axon
- Peak membrane potential during an AP remains consistenly depolarized
- AP Propagation takes time (to charge membrane)
- Myelination increases conduction velocity
What causes depolarization to attenuate as it moves down the axon?
Concept 1: Propagated Depolarization
Resistance
Specifically:
- Membrane resistance (Rm)
- Interaxonal resistance (Ri)
Explain:
Membrane resistance (Rm)
Interaxonal resistance (Ri)
- Membrane resistance (Rm): A function of the number of open ion channels (resistance to the loss of ions)
- Interaxonal resistance (Ri): A function of the diameter of the axon (resistance ions experience as they flow down the axon, e.g dyenin)
Explain the Length Constant (ƛ)
Length constant (ƛ) is the distance it takes for the AP to 37% of Vmax
What is the length constant (ƛ) equation and relationship to Rm and Ri?
- Equation: ƛ=(Rm/Ri)^1/2 or ƛ= √Rm/Ri
- Directly proportional to Rm
- Inversely propotional to Ri
Explain why a HIGH length constant is positive?
The greater the value of the length constant, the farther the potential will travel
What outcomes of Rm and Ri are needed for a high length constant and explain why?
- High Rm: prevents the loss of ions/voltage through the membrane
- Low Ri: prevents voltage from decreasing as it travels down the axon
What causes the peak membrane potential along an axon during an AP to remain consistenly depolarized?
Concept 2: Propagated Depolarization
Refractory periods
Explain the two types of refractory periods
- Absolute: A 2nd action potential can NOT fire (Na+ channels can not be reactivated-either in open or inactivated state)
- Relative: A much greater depolarization required for an AP to fire (Active K+ channels hyperpolarizing the cell)
Why is time important in action potential propagation?
Concept 3: Propagated Depolarization
- Time is needed for the membrane to charge as the action potential moves along the axon= Rate limiting event of AP propagation
Explain the Time Constant (t)
Time constant (t) is the time it takes for the change in Vm to reach 63% of its final form
What is the time constant (t) equation and its relationship to Rm (membrane resistance) and Cm (membrane capacitance)?
- Equation: t=RmCm
- Directly proportional to Rm
- Directly proportional to Cm
Cm (Membrane capacitance)-ability to store charge
The greater the size of the axon the______
Greater the time it takes for the mebrane to charge
How does myelination increase the conduction velocity?
Concept 4: Propagated Depolarization
- Increases Rm–>Increase length constant (ƛ)
- Decreasing Cm–>Decreases time constant (t)
How are resistors and capicators added in series?
Concept 4
- Rm= R1+R2+ R3….
- Cm= 1/C1+1/C2+1/C3…
Define Saltatory Conduction
- (from Latin saltare, to leap): the propagation of the APs along myelinated axons from one node of Ranvier to the next node
What does myelination do to:
- Membrane resistance
- Membrance capacitance
- Membrane permeability
- Conduction velocity
- Length constant
- Increase membrane resistance
- Decreases membrane capaciance (at myelination site)
- Decreases membrane permeability
- Increases conduction velocity
- Increase length constant
Explain the differences btw unmyelinated axon vs myelinated axons
- Unmyelinated
-Slower conduction
-Local current flow (electrotonic conduction) - Myelinated
-Faster conduction
-Saltatory conduction
-Action potential jumps from node to node
Explain Multiple Sclerosis
Is an autoimmune, degenerative disease of axon demyelination
What are the effects of axon demyelination?
- Increases passive current flow
- Decreases AP conduction velocity
- Which segment of the voltage-gated K+ channel is responsible for detecting voltage changes in the neuronal membrane?
A. S1
B. S2
C. S3
D. S4
d. S4
- Which of the following correctly describes the movement of ions during the repolarization phase of a neuronal action potential?
A. Na+ influx; K+ efflux
B. Only K+ efflux
C. Na+ efflux; K+ influx
D. Only Na+ efflux
b. Only K+ efflux
- The length constant (λ) is the distance it takes to reach 37% of Vmax. Which of the following conditions would lead to an increased length constant?
A. High Rm; Low Ri
B. Low Rm; Low Ri
C. Low Rm; High Ri
D. High Rm; High Ri
a. High Rm; Low Ri
- Scientists at the Morsani College of Medicine are conducting genetic testing on neuronal membranes. Which of the following mutations would likely lead to an increase in the time necessary to charge a membrane?
A. Decreased Rm
B. Increased axonal size
C. Decreased Cm
D. Increased Ri
b. increased axonal size
- Saltatory conduction is defined as the propagation of action potentials from _________ to _________.
A. axon hillock; dendrite
B. dendrite; node of ranvier
C. dendrite; axon hillock
D. node of ranvier; node of ranvier
d. node of ranvier; node of ranvier