1/3 Britton Neuronal Action Potentials Flashcards
_____ separates the ICF and ECF compartments
Plasma membrane
Plasma membrane consists of:
- phospholipid bilayer
- Membrane bound proteins that permit communication (ion channels, transporters, receptors)
Transport of ions and small H2O-soluble molecules across the cell membrane requires:
Membrane transport proteins
Types of membrane transport pathways
- simple diffusion
- facilitated diffusion
- active transport
Examples of plasma membrane transporters
- ion channels
- ATP dependent pumps
- carrier proteins
- channel proteins
Carrier proteins are used for:
- facilitated diffusion
- active transport
Channel proteins are used for:
Simple diffusion
Approximate concentration of Na+ (in/out)
- Outside: 140
- Inside: 14
Approximate concentration of K+ (in/out)
- Outside: 4
- Inside: 120
Approximate concentration of Cl- (in/out)
- Outside: 105
- Inside: 10
Approximate concentration of Ca2+ (in/out)
- Outside: 2.5
- Inside: <1
A fluid that is composed of 120 mM K+, 12 mM Na+, and 15 mM Cl- but is virtually Ca2+ free would best approximate which body fluid compartment?
Intracellular
Excitable cells have the ability to be ____
electrically excited
Examples of excitable cells
- neurons
- muscle cells (skeletal, cardiac, smooth)
- some endocrine cells (pancreatic beta cells)
Mnemonic: MEN are easily excited (muscle, endocrine, neuron)
Excitable cells have an ______ across the cell membrane
Electrical potential difference
What is an electrical potential difference?
A charge difference
Electrical potential difference between inside and outside of the cell is called:
Membrane potential (Vm)
Membrane potential is a function of:
relative permeability for K+ versus Na+
Whether the channels are opened or closed
Membrane potential values depend on _____ and can range from ____
Cell type; -30 to -90 mV
Membrane potential of a nerve cell at rest is generally:
-70 mV
How is membrane potential measured?
Via inserting a small recording microelectrode inside the cell to measure the potential difference across cell membrane
Membrane potential is always expressed as:
Voltage inside the cell relative to the outside
-20 mV means inside is negative compared to the outside
Membrane potential is determined by several factors, which are:
- concentration of +/- ions across the cell membrane
- membrane pumps and transporters that transport ions across the cell membrane
- relative permeability of cell membrane to these ions (open or closed channels)
Example of a key membrane transporter
Na+/K+ ATPase
______ establishes the concentration gradient for Na+ and K+ ions and is important for maintaining ______
Na+/K+ ATPase; cell resting potential
Na+/K+ ATPase pumps out ____ and pumps in ____
3 Na+; 2 K+
What is digoxin used to treat?
Heart failure
Examples of drugs that target Na+/K+ ATPase
- Digoxin
- Ouabain
- Digitalis glycosides
Disrupts Na+/Ca2+ exchanger as a result
Ion channels are membrane proteins that span the plasma membrane _____
Repeatedly
Ion channels have distinct structural features, including:
- Pore through which ions can diffuse across the membrane
- Several transmembrane domains
- Selectivity filter
True or false: ion channels allow many different ions to pass through
False - they are selective for a particular ion, uses a selectivity filter
Ion channels are gated by a mechanism that _____
Opens or closes the channel pore
Gating mechanisms that open and close channels
- Voltage-gated
- Ligand-gated
- Mechanically-gated
Voltage-gated ion channels open by:
Changes in membrane voltage
Ligand-gated ion channels open after:
Binding of a ligand to a receptor site on the channel
Mechanically-gated ion channels open with:
Membrane stretch
Ion channels control the ______ to ions and thus play a primary role in ______
Membrane permeability; the electrical behavior of excitable cells
Voltage gated Na+ channels have ____ gates, which are:
2; activation and inactivation gate
In an open-state voltage gated Na+ channel:
Na+ ions flow down electrochemical gradient
Na+ channels exist in what 3 states during the phases of the action potential?
- rested-closed
- activated-open
- inactivated-closed
______ is the driving force for ion movement across the cell membrane
Electrochemical gradient
Electrochemical gradient consists of what 2 forces?
- Chemical gradient
- Electrical gradient
A chemical gradient is present when there is:
A difference in concentration of a chemical across a membrane
An electrical gradient is present when there is:
Difference in charge across a membrane
At electrochemical equilibrium:
Chemical and electrical driving forces acting on an ion are balanced
True or false: there is no further diffusion of an ion across the membrane when electrochemical equilibrium is reached
True (and even if channel is open)
How can we calculate equilibrium potential for a particular ion?
- Nernst equation/potential
- need [ICF] and [ECF]
What is the equilibrium potential for Na+?
+60 mV
What is the equilibrium potential for K+?
-90 mV
What is the equilibrium potential for Ca2+?
+130 mV
What is the equilibrium potential for Cl-?
-63 mV (but can vary)
The resting membrane potential of nerve cells is ____ and is close to the equilibrium potential of what ion?
-70 mV; K+
Action potentials are _____ signals, often called _____
Electrical; electrical impulses
____ are the basis of information transfer in nerves
Electrical signals (AP’s)
Examples of electrical signals
- transmit sensory information
- initiate an action like contraction of a muscle or secretion from a gland
Think about afferent and efferent (sensory and motor)
An action potential is a ____ in membrane potential and goes from _____ to ____ and back to _____
Transient change; negative to positive; negative
In nerves, during an AP, Vm changes from resting Vm ____ to ____, termed a _______
-70 mV; +30 mV; depolarization
After an AP is initiated, Vm returns to resting negative value after _____. Termed _____
1 msec; repolarization
_____ are active responses generated by changes in the permeability of the neuronal membrane
AP’s
In the resting state for neurons, Na+ channels are ____. K+ channels are ______
Closed; open
Efflux of K+ ions making inside negative (resting Vm close to Ek)
What happens to a neuron when it becomes excited by a stimulus?
- Na+ channels open and cause rapid influx of Na+ ions into the cell
- positive charge movement into the cell causes a depolarization and inside of cell is now +30 mV
When Na+ channels open during an AP, why is there a rapid influx of Na+?
- Concentration gradient (less Na+ inside)
- Electrical gradient (inside is negative at rest, attracts positive Na+)
After a depolarization during an AP, Na+ channels _____ after 1 msec. But, ____ are open and additional _____ now open. ____ flows out of the cell according to their ______, creating a ____ potential inside the cell, termed a _____
Close (inactivate); K+ channels; voltage-gated K+ channels; K+; electrochemical gradient; negative; repolarization
During repolarization, what happens to the membrane potential?
Moves back to resting Vm -70 mV and even beyond (hyperpolarization)
Why does hyperpolarization occur?
Because of additional movement of K+ through voltage gated K+ channels
Once the voltage gated K+ channels close after an AP, the membrane will return to the resting potential maintained initially by ____
K+ leak channels
______ is a change more positive than the resting membrane potential
Depolarization
____ is when the membrane potential becomes more negative than the resting membrane potential
Hyperpolarization
____ is the return of the membrane potential towards resting Vm following either depolarization or hyperpolarization
Repolarization
_____ is the level to which membrane potential must be depolarized to initiate an action potential
Threshold potential
Explain the characteristic phases of an action potential due to specific changes in the membrane permeability to Na+ and K+
- K+ leak channels maintain resting potential
- upon stimulus, K+ channels close and Na+ channels open to cause depolarization
- Na+ channels close, K+ channels reopen and open voltage gated K+ channels (repolarization/hyperpolarization)
- Voltage-gated K+ channels close, K+ leak stays open to maintain resting Vm
True or false: AP’s have a threshold potential for activation
True
For a typical neuron, the threshold potential is near ____
-55 mV
For activation gates of Na+ channels to open, there needs to be ______
Sufficient current that exceeds threshold potential
True or false: small depolarizations that do not reach threshold may result in an AP
False - do not (all or nothing principle)
The intensity of a stimulus is encoded in ____, not _____
Frequency of AP’s; AP amplitude
True or false: bigger stimuli elicit a bigger AP
FALSE - do not change AP amplitude!
The amplitude of an AP is independent of _____
Magnitude of the stimulus used to evoke it
Multiple AP’s with increased frequency occur when:
the intensity or duration of a stimulus is reached
Absolute refractory period
Interval of time during an AP in which another AP absolutely cannot be generated
Why is there an absolute refractory period?
Na+ channels inactivate after opening, and are unable to open again until the gate is reset
In a relative refractory period, a 2nd AP can be initiated, but:
Will require a greater stimulus than before
How do AP’s move along the axon?
They are propagated
AP is generated at the ___ and propagates along the ____
Axon hillock; axon
How does axon propagation occur?
- Current that flow inward at a point on the axon during an AP spread out along the axon and depolarize the adjacent sections of the axon membrane
- when this depolarization reaches threshold, a new AP is generated at the new location
AP propagation cannot reverse direction due to:
Refractory periods
____ and ____ affect AP conduction speed
Axon diameter and myelination
Larger diameter axons have a ____ AP conduction velocity due to _____ for ion flow during AP propagation
Faster; less resistance
Myelinated axons have a ____ AP conduction velocity as APs are propagated from ____ to _____
Faster; Node to node of ranvier
Can ions flow through myelin sheath?
No
Can ions flow through the node of ranvier?
Yes, with ease
What is concentrated at nodes of Ranvier?
Na+ and K+ channels
In myelinated axons, APs are propagated from node to node rather than conducting along the whole nerve membrane. This is termed _____
Saltatory conduction
Why is saltatory conductance of value?
- conduction is faster
- conserves energy for the axon (less energy required via Na+/K+ pump)
Multiple sclerosis
- degeneration of myelin sheath
- decrease in nerve transmission
Nerve fibers are often classified according to their:
Conduction velocity
Order of fastest to slowest nerve fibers
- A alpha
- A beta
- A gamma
- A delta
- B
- C
Which nerve fiber is not myelinated
C
Large axon diameter and myelination result in _____ conduction velocities
Faster
A-type nerve fibers are mostly involved in:
Sensory and motor functions
Several drugs inhibit nerve excitability, such as:
- Local anesthetics
- Tetrodotoxin (TTX)
- a-toxins and beta-toxins
- Batrachotoxin
Examples of local anesthetics
- lidocaine
- procaine
- tetracaine
What is tetrodotoxin?
- potent neurotoxin
- found in pufferfish and blue-ringed octopus
a- and beta-toxins come from:
Scorpion venom
Batrachotoxin comes from:
S. American frogs “poison dart” of Indian arrows
Local anesthetic prevents or relieves pain by:
Interrupting nerve conduction
Most local anesthetics act directly on:
Activation gates of Na+ channels
LA’s make it difficult for ____ to open, thereby reducing ____
Na+ channels; membrane excitability
Partial or full blockade of Na+ channels will result in:
- decrease in the magnitude of depolarizing Na+ current
- increase in threshold for firing an AP
As the number of Na+ channels blocked by LA channels increases, _____ slows
AP propagation
True or false: LA inhibition of Na+ channels is reversible
True
In use of local anesthetics, AP conduction fails when:
Depolarizing current preceding the propagated AP is insufficient to reach threshold in the adjacent patch of nerve membrane
True or false: All nerves are blocked equally by LA’s
False
LA sensitivity may depend on multiple factors, such as:
- Myelination
- Axon diameter
- level of nerve activity
- Nerve function
- Differences in density of ion channels or location of a nerve fiber within a large nerve trunk
In general, myelinated axons are _____ to LA blockade than unmyelinated axons
More sensitive
____ diameter axons are more sensitive to LA action
Smaller
Nerves with ____ firing rates are more sensitive to LA blockade
Higher (LA may get better access to Na+ channel when in activated state)
LA blockade may be stronger in sensory or motor nerves?
Sensory nerves (tend to fire APs at higher frequencies compared to motor nerves)
Motor fibers are often located in the ___ portion of the bundle and are more or less accessible to LA?
Outer; More
motor fibers may be blocked before sensory fibers in large mixed nerves
_____ is usually the first modality to disappear after LA injection
Pain
LA produces an orderly progression of loss of:
- temperature sensation
- proprioception
- sensation
- light touch
- motor function
Variation among patients and different nerves is considerable
