1: Action Potentials Flashcards
Define capacitance. What do capacitors do? How does capacitance affect speed of membrane potential changes along an axon?
Capacitance: occurs whenever conducting materials are separated by insulating material (thinner insulator = more capacitance)
Capacitors store charges of opposite sign on opposing surfaces
Membrane capacitance slows time course of voltage changes
-Results in gradual, rather than sharp, change in ionic current/membrane potential
How does myelination affect membrane capacitance and length constant?
Myelination DECREASES membrane capacitance and therefore INCREASES speed and INCREASES length constant
Name several of the most widely known reagents that block the activity of voltage-gated ion channels. (5)
Tetrodotoxin (from pufferfish) and saxitoxin (from red algae): blocks Na channels
Conus toxins (from fish-eating snails): blocks Ca channels
Tetraethylammonium (TEA): blocks K channels
Lidocaine: blocks Na channels
Illustrate the 4 different phases of action potentials and correlate them with the types of ion channels that are active during them.
- Depolarizing/rising phase: MP approaches equilibrium for Na ions
- Voltage-gated Na channels are open - Overshoot: MP may become positive
- Voltage-gated Na channels still open - Repolarizing phase: MP rapidly becomes more negative
- Na channels are closed and inactive, “delayed rectifier” K channels are open - Hyperpolarizing phase: MP becomes more negative than it was originally
- “Delayed rectifier” K channels are open, then close
Explain how HCN channels and A current K channels can influence the frequency of firing in rhythmically active cells.
HCN channels: hyperpolarization, cyclic nucleotide-gated channels
- Open upon strong hyperpolarization
- Cation-selective: Na ions go in
- Drive membrane potential to threshold
- Important in rhythmically active, pacemaking cells
“A current” K channels prolong interspike interval between APs
- Open upon depolarization -> counteract depolarization
- Rapid inactivation
- Only a few, so don’t prevent AP, but do DELAY reaching threshold
Illustrate how action potentials propagate along an axon.
Involves both active and passive spread
Active depolarization -> passive spread to next channel -> active depolarization and so on
Describe how myelination occurs in the CNS and PNS, including the cell types thought to play important roles.
CNS: individual oligodendrocytes form myelin sheaths around multiple axons
-Myelin genes unaffected by axon presence or absence
PNS: individual Schwann cells form myelin sheaths around one axon (myelinated), or loose wraps around multiple axons (unmyelinated)
-Myelin gene expression depends upon axonal contact
Illustrate how saltatory conduction occurs and why it is advantageous (2).
Nodes of Ranvier: uncovered regions of the axon membrane between myelin sheath
-Have high concentration of Na channels
APs only regenerated at nodes of Ranvier, spreads passively in between nodes
-“Jumps” from node to node rather than regenerating at all points along the axon
- Increased velocity
- Metabolically more efficient: less ATPase activity needed because ion flow is only at nodes
Explain how demyelinating diseases can slow and even prevent the propagation of action potentials along an axon. (3)
Demyelinating diseases: segments of myelin absent
- Slow/prevent propagation by increasing capacitance (decrease rate of depolarization) and decreasing membrane resistance (shorter length constant)
- —May result in failure of AP to be propagated if depolarization at next excitable region doesn’t reach AP threshold
- Guillain-Barre syndrome: loss of PNS myelin due to immune response
- Multiple sclerosis: loss of CNS myelin, involves autoimmune response
- Get formation of astrocyte scars/plaques
- No treatment available, use immunosuppressives - Charcot-Marie-Tooth syndrome: myelin loss from mutation in gap junctions connecting the cytoplasm of the different layers of myelin
Define membrane time constant. How does it relate to the concept of temporal summation?
Time to reach 63% of total potential charge (rather, to decay to 37% of original potential change)
Important for temporal summation
- Stimuli too small by themselves can add up if the stimulus interval is shorter than the time constant
- Longer time constant = more potential for temporal summation
What is the length constant? How does it relate to spatial summation?
The distance at which 37% of the original change in membrane potential still occurs
Receptor potentials will summate if they are within the length constant
How do capacitance and axon diameter relate to speed of propagation?
Capacitance is INVERSELY proportional to speed of propagation (thinner membrane = higher capacitance = lower speed)
Axon diameter is DIRECTLY proportional to speed of propagation (larger diameter = higher speed)
Define action potential.
A rapid depolarization and then repolarization of the membrane in response to a membrane depolarization of sufficient magnitude
Define threshold potential. Why are APs “all or none”?
The membrane potential at which the inward current through the Na channels that are opening up is finally greater than the outward K current through other channels
All or none because reaching this threshold -> very rapid positive feedback cycle (more Na channels open)
Define refractory period.
A period of time in which another AP cannot be generated or can only be generated with some difficulty
What are the two refractory periods and what causes each?
Absolute refractory period: impossible to generate another AP
–Na channels are inactivated
Relative refractory period: AP can be elicited, but requires a stronger stimulus
–Residual K channel activity counteracts depolarization
True/false: The activity of the Na/K ATPase plays an important role in the time course of an AP
FALSE!
Proportion of ions that move during an AP is very small
Describe the structural features of voltage-gated ion channels that are responsible for their ion selectivity.
Ion selectivity: determined by pore loops (selectivity filter)
- Select for size (hydrated radius) and hydration energy (more E required to strip water from small ion)
- AAs on tips of pore loops are key
Describe the structural features of voltage-gated ion channels that are responsible for their voltage-gated activation.
Activation: determined by S4 voltage sensors
- Channels rapidly open, “all or none”
- Charged residues (arg, lys) in S4 TM region -> “helical twist” outward when inside becomes positive
Describe the structural features of voltage-gated ion channels that are responsible for their inactivation.
Inactivation: determined by intracellular loops and AA clusters
- K has “Ball and chain”: (+) charge group of AA plugs channel like a bathtub stopper
- Na and Ca channels have (+) charged AA cluster on loop that flips up and inactivates the channel
What is a Ca shoulder?
A plateau in the repolarization phase of an AP
Results from a delayed rate of repolarization due to slowly inactivating Ca channels
—Ca influx keeps cell somewhat depolarized
Important in NT release
Give two examples of the role of ion channels in disorders.
Neuromas (severed nerve -> tangle of axons) -> (phantom) pain through increased Na channel expression
Channelopathies -> epilepsies/seizures
How is backpropagation prevented?
The part of the axon that was just traversed is in the refractory period and cannot initiate a regenerative response
What is the AIS?
Axon initial segment, or axon hillock
Initial part of axon next to the cell body; site of AP generation
Separates axonal compartment of cell from somatodendritic compartment
Describe 5 proteins thought to play important roles in myelination.
- Neuregulin (NRG): from axon; regulates number of layers of myelin sheath
- More layers for larger axons - Myelin associated protein (MAG): initial axon/glia recognition/adhesion
- Po: over 50% of protein in PNS myelin
- Mediates myelin compaction - Proteolipid protein (PLP): over 50% of protein in CNS myelin
- Mediates myelin compaction - Myelin basic protein (MBP): along inner surface of membrane
- Mediates myelin compaction
Briefly, describe the therapeutic use of oligodendrocyte transplantation.
Used to remyelinate CNS axons in experimental models
-Problem = thinner myelin than the original sheath
