Action Potentials Flashcards
What are action potentials?
- A rapid increase then decrease in Vm
- Also known as AP, spike, neural impulse
- An ‘all-or-none’ event (i.e. action potentials from a given neuron are all the same)
Direction of AP on axon diagram
Why are action potentials needed?
- Axons are often long – neurons can be huge cells! (not all neurons need APs, but most do)
giraffes: several meters
blue whales: 25 m. from fluke to brain sauropod dinosaur: 40–50 m. from tail to brain - Axoplasm is a poor conductor of electricity axoplasm is ~107 worse conductor of
electricity than copper wire
a 1m. long axon that is 1 μm in diameter has an electrical resistance equal to 1010 miles of 22 gauge copper wire (10 times the earth-Saturn distance) - Axons are leaky and passive potentials don’t conduct very far
Leaky axons and conduction
The Action Potential and its Phases
- If a neuron is only slightly depolarized, it may not initiate an action potential
- For an action potential to start, the axon hillock must be sufficiently depolarized to reach ‘threshold’ (about -40 mV)
Diagram of AP phases
Initiating an action potential
- AP threshold is about -40mV
How does a neuron get depolarized to reach the AP threshold?
1. Sensory input - physical energy leads to change in Vm (transduction) e.g. pressure from thumbtack opens Na+ channels (each sensory system has unique mechanisms)
2. Neurotransmitter from other neurons
Depolarization and firing rate
Information is coded in firing rate
- Neurons in different parts of the brain respond to different sensory inputs, memories, emotions, etc.
- Even within one area of the brain, different cells respond with greater or fewer action potentials to different inputs
How is an action potential generated?
Answer: three ion channels are involved
- Potassium channels that are open regardless of membrane potential (i.e. they always ‘leak’
- Voltage-gated sodium channels
- Voltage-gated potassium channel
What does ‘voltage-gated’ mean?
That a channel changes shape and the pore can pass ions only at certain membrane potentials (usually depolarizatoin)
Leakage K+ channels
- K+ constantly leaks out of axons
- Largely responsible for resting potential (membrane is 40x more permeable to K+ than Na+ at rest
Two things are always happening at the cell membrane
1. Na+/K+ pump
2. K+ leakage
Voltage-gated Na+ and K+ ion channels
- These channels are located in axon membranes
- There is a high concentration of voltage-gated Na and K channels at the axon hillock (spike initiation zone) and at gaps in myelination
Voltage-gated sodium channels
- Membrane depolarization alters channel shape
- Channels open when the membrane is depolarized
- Positive feedback: more open NaV channels increases Vm, opening more channels, etc.
- Vm rapidly increases –> rising phase
Opening and closing of NaV channels
- Depolarization makes NaV channels open and then they automatically close
Depolarize the membrane and keep it depolarized for seconds
Three NaV channel examples:
* Channels open at slightly different times
* Na+ flows inward
* Channels automatically close after about 1 ms
* Channels stay closed even though membrane stays depolarized (like a screen door with a spring automatically closes)
The voltage-gated sodium channel has ___ states
3
What are the 3 states of the NaV channel?
Open, inactivated, and closed
A protein plug can block ion flow even when the channel is open i.e. ion flow can be blocked two ways:
1. channel is closed
2. channel is open but pore plugged (i.e. inactivated)
Flow chart of three states of voltage-gated sodium channel
Voltage-gated KV channel
- Kv channels are simply open or closed
- After membrane depolarization, Kv channels open about 1 ms slower than Nav channels
- Kv channels are called “delayed rectifiers”
- The addition of open Kv channels to K+ leakage channels, makes Vm decrease rapidly
->falling phase
How do Kv and Nav channels differ after depolarization?
Kv channels open about 1ms slower than Nav channels
What are Kv channels called?
Delayed rectifyers
How does the addition of open Kv channels to K+ leakage channels affect Vm
It makes it decrease rapidly (falling phase)
What two factors determine ion flow?
Conductance and driving force
How do conductance and driving force determine ion flow
Action potential shape results from changes in Nav and Kv conductances
When the AP starts, the Na+ conductance is ___ and the membrane moves towards the ___
High
Sodium equilibrium point
Later, K+ conductance is high and the membrane moves towards the ___
Potassium equilibrium point
Resting state of AP
Vm = -65 mV
- Na+/K+ pump always running
- K+ leakage channels always open
- Vm is closer to EK than ENa because the membrane is much more permeable to K+
Depolarization of AP
Vm = -65 to -40 mV
Initial depolarization occurs through:
- Sensory stimuli
- Neurotransmission
Threshold of AP
Vm = -65 to -40 mV
- Membrane depolarization increases the probability that Na+ channels will open (even below -40mV)
- Greater depolarization from -65 to -40mV makes more channels open and more Na+ flows into neuron
- If the depolarization exceeds -40mV, the inward flow of Na+ exceeds the outward K+ current from leakage and slow Kv opening. This is threshold - the essential trigger for an action potential
- Above threshold, positive feedback rapidly accelerates Na+ current
What happens if the depolarization exceeds -40mV?
- The inward flow of Na+ exceeds the outward K+ current from leakage and slow Kv opening
- This is threshold - the essential trigger for an action potential
Rising phase
Vm above threshold and increasing to 40 mV
- Voltage-gated Na+ channels (Nav) continue to activate
- High sodium conductance (gNa»_space; gK)
- Sodium rapidly enters cell
- Vm moves upward towards ENa (62mV)
- Driving force on Na+ decreases
- Driving force on K+ increases
Overshoot
Vm peaks around +40 mV
As Vm gets closer and closer to ENa:
- Driving force on Na+ decreases
- NaV channels quickly inactivate
- KV channels continue to open after a delayed start (high gk)
- Vm never reaches ENa (62 mV) because there is always K+ leaving the neuron)
- Large driving force on K+
Falling phase
Vm moves down toward Ek
- NaV channels continue inactivating
- Kv channels continue to open
- Vm approaches Ek
- Driving force on Na+ increases, but Na+ can’t cross the membrane because channels are inactivated
- Driving force on K+ decreases
- gK»_space; gNa
Undershoot and return to resting potential
Vm moves below -65 mV (closer to EK) then returns to -65mV
- Vm dips below -65mV because there are Kv AND Kleak channels open
- NaV channels are inactivated and then de-inactivate (ready to fire another AP)
- Kv channels close and Vm increases back to -65mV
Absolute refractory period
- The majority of NaV channels are inactivated and cannot open
- New action potential impossible
Is a new action potential possible in the absolute refractory period?
NAUR
Relative refractory period
- A sufficient number of Nav channels are de-inactivated (ready to open), such that an action potential can occur if sufficient depolarization
- Greater depolarizatoin than normal is required to reach threshold and produce AP
Is a new AP possible in the relative refractory period?
Yes, but a greater depolarization than normal is required to reach threshold and produce AP
Ion channel genes and neurological disease
Many types of neurological disorders can result from ion channel mutations that affect action potentials:
e.g. migraine, epilepsy, deafness, paralysis, ataxia (lack of muscle coordination)
Episodic ataxia type 1
In a mouse model, a single stimulus leads to reverberant action potentials
Rare Diseases based on Ion Channel Mutations
- Generalized epilepsy with febrile seizures
- Benign familial neonatal convulsion
- Episodic ataxia
Generalized epilepsy with febrile seizures
- Seizures start in early childhood
- Na+ channel mutations, slow Nav inactivation
- Neurons are hyperexcitable
Benign familial neonatal convulsion
- Frequent brief seizures
- K+ channel mutations, reduced K+ current in falling phase
- Neurons are hyperexcitable
Episodic ataxia
- Episodes of poor coordination of movement and balance (ataxia)
- Various K+ channel mutations impair AP repolarization
Ion channel toxins
- Tetrodatoxin (TTX)
- Saxitoxin (STX)
Tetrodatoxin (TTX)
- Puffer fish (“fugu”) ovaries, liver, intestines (from ingested bacteria)
- 23 people have died since 2000 in Japan from fugu consumption
- x1200 more toxic than cyanide and no antidote
- blocks Na+ channels and stops action potentials (1mg is lethal)
- muscle paralysis -> asphyxiation
- TTX is a useful tool for studying the role of Na+ channels
TTX is a useful tool for studying the role of ___
Na+ channels
Saxitoxin (STX)
- People are poisoned by eating shell fish that have
ingested dinoflaggelates (algae – red tide) - x100 more lethal than sarin nerve gas
- 0.2 mg lethal in humans
- CIA suicide pills
- also blocks Na+ channels and action potential
STX blocks ___ and ___
Na+ channels and action potentials
Local anesthetics
- Locally and transiently block APs
- The first discovered was cocaine
- Coca-cola was made from alcohol + cocaine from cocoa leaves
Mechanism of local anesthetics
- Most widely used now is lidocaine
- Blocks Na+ channels that are open or inactivated (not closed/de-inactivated)
- APs in small axons are most affected because their Na+ channels must open to assure AP propagation
- Luckily for us, nerves responsible for pain have small axons
Action potential propagation
- To affect other neurons, the AP generated at the axon hillock must propagate to the axon terminal and synapse
- The inflow of Na+ that happens in an AP will depolarize neighboring patches of membrane to threshold
- Propagation only one way down axon because the soma-side of the axon is refractory
Myelination
- Larger axons conduct action potentials faster
- Myelination also speeds propagation without size increase
- Ion channels concentrated at nodes of Ranvier
- Myelin helps current flow down axon by blocking leakage and lowering axial resistance
- Nodes spaced such that Na+ influx quickly reaches next node and AP jumps node-to-node
- Saltatory conduction (“to leap”)
Multiple Sclerosis
- Autoimmune attack on myelin degrades AP conduction
- Age of onset: 20-40
- Genetics:
-women 3-4 times as likely as men
-siblings 5%
-identical twins 31% - Environmental factors – living closer to the geographic poles, low vitamin D, smoking
Multiple sclerosis symptoms
- Blurred vision is often the first symptom
- Limb numbness or weakness
- Electric shock sensations
- Fatigue
Voltage-gated sodium channels inactivate automatically ___ after they open
About 1 msec
What is the duration of an action potential?
About 2msec
In the relative refractory period, more __ than __ channels are open
More K+ than Na+
Changes in all of the following play a significant role in the transition from the falling phase through the undershoot and back to the resting membrane potential EXCEPT:
a) voltage-gated potassium channels
b) voltage-gated sodium channels
c) the sodium/potassium pump
c) The sodium/potassium pump
What state are NaV channels in during the absolute refractory period?
Inactivated
In the absolute refractory period, significant numbers of ___ and ___ are open
Kleak and Kv
GABA is an inhibitory neurotransmitter because it causes __
Entry of Cl- into neurons, which causes hyperpolarization
