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Action Potentials
UC MED 2015
99
Medical
Graduate
11/18/2011

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Term
During signaling, the membrane potential does not stay constant at the RMP but changes briefly, these brief changes are known as
Definition
action potentials
Term
How do you measure an action potential?
Definition
with an electrode fabricated in the lab and then penetrate the cell and measure compared to outside of the cell which is zero. Follow membrane depolarization as they happen
Term
What are the general features of an AP?
Definition
1) Threshold
2) Depolarization
3) Overshoot
4) Repolarization
5) Afterpotential
6) Resting Potential
Term
What are the major players in the AP?
Definition
Voltage gated Na+ channel
Voltage gated K+ channel
Term
The Na channel can assume, how many conformations?
Definition
3
Term
For the Na channel, what is transient above threshold depolarization?
Definition
Fast inactivation
Term
For the Na channel, what is the steady subthreshold depolarization, RMP to t.p. called?
Definition
Slow inactivation- important for modulating neurons
Term
At rest the K+ voltage-dependent channel is?
Definition
closed
Term
When a Na+ or K+ channel opens, which DIRECTION will the ions flow?
Definition
The DIRECTION depends on the energy difference
between Em and the equilibrium potential for each ion.
Term
the energy difference between Em and the equilibrium potential for each ion, this difference is called?
Definition
driving force
Term
Ion movement during AP can be measured either as...
Definition
Fluxes or Currents
Term
After an AP, what restores the ion gradients?
Definition
Na/K pump
Term
What is the period where the cell can not fire, since the Na+ channels have not returned to their resting state from the the inactive state?
Definition
Refractory Period
Term
What are the two stage of the refractory period?
Definition
ARP-no stimulus can cause an action potential
RRP- an action potential can occur since enough Na+ channels are ready to go, but Resting potential hasn't occurred yet
Term
What is the ability or readiness of a nerve or muscle to fire an AP?
Definition
Excitability
Term
How do cells modulate their RMP to respond to different conditions?
Definition
Typically, by having resting K+ channels whose activity
is regulated by cellular metabolites, hormones or neurotransmitters.

This alters PNa/PK ratio which in turn alters the RMP
Term
A cell with a LESS negative RMP is...
Definition
Less likely to fire an AP
Term
A cell with a MORE negative RMP is...
Definition
MORE likely to fire an AP
Term
Sodium channels can only open from the?
Definition
closed state
Term
Ca2+ entry is...
Definition
DEpolarizing, same direction as Na+ entry
Term
In the heart ventricle, ___a____ influx starts the depolarization and ___b___ influx keeps it going
Definition
a-Na+
b-Ca2+
Term
Some cells also use, what to REPOLARIZE the AP?
Definition
Cl-
Term
Cl- ion s move _____ the cell for repolarization
Definition
into
Term
How is an AP initiated on the cell membrane?
Definition
A local depolarization brings one area of membrane to TP
Term
On avg, the RMP of a nerve membrane is more depolarized (-70mV) than the RMP of skeletal muscle (-90mV)? Which cell is better positioned to modulate excitability?
Definition
Nerve- it can move up or down, the muscle can't move much lower so it is ready to respond
Term
THREE ways a depolarization can spread along a membrane from the site of stimulus
Definition
-Passive Spread (NO Na+ channels)-fast
-Active Propagation (Na+ channels)- faster
-Saltatory Conduction (Na+ channels, myelin)- fastest
Term
In PASSIVE CONDUCTION, AMPLITUDE of the depolarization ____________ with distance along the axon
Definition
Decreases
Term
What type of conduction occurs in the synapse and cell body?
Definition
Passive conduction
Term
What type of AP occurs in the Axon hillock and axon?
Definition
Active Propagation
Term
What is a fatty white substance (essentially layers of membrane) produced by glial cells?
Definition
myelin
Term
When you separate charges, you...
Definition
store electrical energy
Term
The amount of energy stored is measured in?
Definition
Volts
Term
What are the two gradients across cell membranes?
Definition
-concentration gradient- generated by the Na/K pump
-electrical gradient- results from separation of charges
Term
The concentration and electrical gradient are called? At equilibrium, these two gradients are __________.
Definition
-Electrochemical gradient
-EQUAL
Term
In terms of K+, at equilibrium there is what two things?
Definition
K+ gradient and opposite electrical gradient
Term
How do many cells signal each other?
Definition
with changes in membrane potentials
Term
During signaling, the membrane potential does not stay constant at the RMP but changes briefly. These brief changes are called?
Definition
Action Potentials
Term
Starting at resting potential, tell me the order of events in an AP?
Definition
1) Resting Potential
2) Signal - that reaches threshold or beyond
3) Depolarization
4) Overshoot
5) Repolarization
6) Afterpotential
7) Resting Potential
Term
What are the two major players in in the Action Potential?
Definition
-Voltage-gated Na+ Channel
-Voltage-gated K+ Channel
Term
What are the three conformations of the Voltage-gated Na+ channel?
Definition
1) resting (closed)
2) inactive (closed)
3) Active (open)
Term
Na channels can only open from which state?
Definition
resting/closed state
Term
Which pathway for the Voltage-gated Na+ channel has a transient above threshold depolarization?
Definition
Fast Inactivation
Term
Which pathway for the Voltage-gated Na+ channel has a steady subthreshold depolarization, RMP to t.p.?
Definition
Slow inactivation
Term
For the fast pathway of the VGNC, return to resting state from inactive state in?
Definition
1-10 ms
Term
In the Slow pathway for the VGNC: resting to inactive conformation without opening in___________, and depolarization in range ___________________?
Definition
- 10-50 ms
- -90 to -50 mV
Term
The Voltage-gated K+ channel, is it the same or a different protein form the resting K+ channel?
Definition
different- it has a resting and an active state
Term
When a Na+ or K+ channel opens, which DIRECTION will the ions flow?
Definition
The DIRECTION depends on the energy difference between Em and the equilibrium potential for each ion
Term
The DIRECTION depends on the energy difference
between Em and the equilibrium potential for each ion. This difference is called the...
Definition
Driving Force
Term
What are two ways to measure ION MOVEMENTS?
Definition
-Current (coulombs per sec per cm2)
- Flux (moles per sec per cm2)
Term
After an AP, what restores the ion gradients?
Definition
Na/K pump
Term
The amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following excitation?
Definition
Refractory period
Term
What is the interval during which a second action potential absolutely cannot be initiated, no matter how large a stimulus is applied?
Definition
Absolute Refractory Period
Term
What is the interval immediately following during which initiation of a second action potential is inhibited but not impossible?
Definition
Relative Refractory Period
Term
What can be modulated for longer times by changing the RMP?
Definition
Excitability
Term
What is the ability or readiness of a nerve or muscle to fire an AP?
Definition
Excitability
Term
Long-term changes in excitability are modulated by changes in the?
Definition
RMP
Term
When the RMP depolarizes (movement up on graph), is the cell less or more excitable?
Definition
less
Term
When the RMP hyperpolarizes (movement down on graph), is the cell less or more excitable?
Definition
more
Term
A cell with a LESS negative RMP is _____ likely to fire an AP
Definition
LESS
Term
A cell with a MORE negative RMP is ______ likely to fire an AP
Definition
MORE
Term
How do cells modulate their RMP to respond to different conditions?
Definition
Typically, by having resting K+ channels whose activity
is regulated by cellular metabolites, hormones or neurotransmitters.

This alters PNa/PK ratio which in turn alters the RMP
Term
Ca2+ entry is ________, same direction as Na+ entry
Definition
DEpolarizing
Term
What depolarizes the SA node of the heart?
Definition
Entry of Ca2+ only, no sodium channels in the SA node
Term
In the heart ventricle, ____ influx starts the depolarization and ____ influx keeps it going.
Definition
-Na+
- Ca2+
Term
What can help repolarize the AP in some cells?
Definition
Cl- channels
Term
Does Cl- move into or out of the cell, when it helps repolarize the membrane?
Definition
moves into
Term
How is an AP initiated on the cell membrane?
Definition
A local depolarization brings one area of the membrane to TP

examples include...
-Post synaptic potentials
-end plate potentials
-pacemaker potentials
Term
IF an ion channel is OPEN and there is a
concentration gradient for the permeant ion,
WILL ION CURRENT FLOW?
Definition
NO, if Em is at the Equilibrium potential for the ion

YES, if Em is away from the Equilibrium potential
Term
What are the three ways a depolarization can spread along a membrane from the site of stimulus?
Definition
-Passive spread- No NA+ channels
- Active Propagation- Na+ channels
- Saltatory Propagation- Na+ channels, myelin
Term
In PASSIVE CONDUCTION, AMPLITUDE of the depolarization IN or DE creases with distance along the axon?
Definition
DEcreases
Term
Myelin is produced by...
Definition
glial cells
Term
Myelin reduces signal loss by acting as an...
Definition
electrical insulator
Term
Myelin speeds conduction velocity by increasing...
Definition
the effective thickness of the membrane
Term
Myelin is found on what part of the axon?
Definition
internode
Term
When the Na+ enters, it is normally attracted...
but myelin has what effect?
Definition
to the negative charges outside the cell, but myelin means that it moves quickly to the next internode where it can make a connection with the outside
Term
What is the diameter (um) and conduction velocity (m/s) in a large myelinated axon?
Definition
- 13-20 um
- 80-120 m/s
Term
What is the diameter (um) and conduction velocity (m/s) in a small myelinated axon?
Definition
- 1-5 um
- 35-75 m/s
Term
What is the diameter (um) and conduction velocity (m/s) in a small unmyelinated afferent nerve?
Definition
- 0.1-0.5 um
- 0.5- 2 m/s
Term
What is the diameter (um) and conduction velocity (m/s) in a mammalian muscle fiber?
Definition
- 40-80 um
- 4.5 m/s
Term
What do Beta cells in the pancreas use to trigger insulin secretion?
Definition
slow changes in RMP
Term
What happens in Beta cells when blood glucose rises?
Definition
1) K+ channels go from open to closed state (ATP binding causes it to close)
2)The cell depolarizes from a higher Na/K ratio
3)membrane reaches potential for Ca2+ channels to open
4)APs are fired in a bursting pattern for 5s
5) Ca2+ entry from the burst causes the secretion of insulin to happen
Term
In Type 2 diabets, what is targeted to help have more insulin secreted?
Definition
Some drugs target KATP receptor, causing it to close for more insulin to be secreted
Term
What is mutated in some forms of Type II diabetes?
Definition
KATP channels
Term
What is is a rare disorder. Normally, type II diabetes has a late onset. These children were found to have a mutation in the Katp channel which prevents it from closing in response to elevated [ATP]i

Gain-of-function mutations in the genes encoding the Kir6.2 (pore forming subunit) and SUR1 subunits of this channel cause neonatal diabetes.

The mutations increase the OPEN time of the channel pore, thereby indirectly producing a marked decrease in the ability of ATP to close the channel.
Definition
Type 2 Diabetes of Infancy
Term
What is a treatment for Type 2 Diabetes of Infancy and how does it work?
Definition
Sulfonylurea drug

This drug directly targets the SUR subunit of the Katp channel and causes the channel to CLOSE.
Term
What disease is characteristic of a muscle contracting normally, but not being able to relax?
Definition
Myotonia Congenita
Term
What EMG is found in a person with Myotonia Congenita?
Definition
"dive-bomber" response
Term
What ) is a disease of action potential generation in skeletal muscle caused by mutations in the muscle Cl channel?
Definition
Myotonia Congenita (Thomsens Disease)
Term
What normally flows with K current to repolarize the membrane?
Definition
Cl-
Term
What happens with a person with Myotonia Congenita?
Definition
1)AP repolarization is slowed when chloride channels are absent
-2)this prolongs repolarization, allows time for some Na channels to recover from inactivation

these Na channels can re-open, when Vm is near threshold

result: probability of firing extra APs
Term
What is the genetic basis of MC (Myotonia Congenita)?
Definition
MC is caused by a mutation in the gene coding for the skeletal muscle Cl
channel. The Cl channel is a large membrane protein with 12 membraning spanning helices (drawn as cylinders in a linear sequence), which assemble to form a central pore. The mutation in MC results in glutamate being substituted for glycine at amino acid 230. Mutant Cl channels cannot conduct Cl- ions.
Term
What is a mutation in voltage-dependent sodium channel?
Definition
HYPERKALEMIC PERIODIC PARALYSIS (HYPP)
Term
What is a disease of action potential generation in skeletal muscle resulting from an abnormal Na channel?
Definition
HYPERKALEMIC PERIODIC PARALYSIS (HYPP)
Term
Tell me more about HYPERKALEMIC PERIODIC PARALYSIS (HYPP)?
Definition
It HYPP is a dominantly inherited disorder of skeletal muscle. Affected individuals experience brief, mild but frequent attacks of muscle weakness. Weakness often develops following a period of rest after exercise and can be provoked by oral K+ loading. During these attacks serum [K+] may rise to 6.0 - 7.0 mM. Some individuals may exhibit signs of muscle membrane hyperexcitability, in the form of clinical and electrical myotonia (repetitive firing).
Term
What happens in HYPP in terms of sodium channels?
Definition
They are even more sluggish in getting to the inactive state, so have residual sodium current , that can drive an AP

-eventually have accumulation of sodium channels in inactive state and this is when the periodic paralysis occurs
Term
What syndrome is due to an immune response to foreign antigens (such as infectious agents produced by campylobacter or influenza virus) that is mistargeted at host nerve tissues instead? The targets of such immune attack are thought to be gangliosides, compounds naturally present in large quantities in human nerve tissues. The end result of such autoimmune attack on the peripheral nerves is damage to the myelin, the fatty insulating layer of the nerve, and a nerve conduction block, leading to a muscle paralysis
Definition
Guillain–Barré syndrome
Term
What general class of disease is this...
When the myelin sheath is damaged, propagation of nerve signals is disrupted and a variety of neurological disorders can result.
Definition
Disorders of myelination, or demyelinating diseases and can be caused by a number of different factors including genetic, autoimmune or viral disease.
Term
What is impaired in MS?
Definition
saltatory conduction
Term
When saltatory conduction is slowed and/or blocked, a plethora of clinical symptoms arise, including...
Definition
Aberrant vision, lack of motor control, and eventually paralysis
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