03_Action Potential_Q and A_Jonathan Flashcards
What is capacitive current?
- Across a capacitor: upon injection of current, initially the increase in positive charges in the cell will cause the accumulation of negative charge on the inside of the membrane to be reduced/dispersed, which leads to the accumulation of positive charges on the outside of the membrane to decline as well.
- the redistribution of charges across the membrane is equivalent to current flow across the membrane, although no carriers of charge (ions) actually cross the membrane
What is ionic current? ((???))
• As the discharging of the capacitor nears completion, more and more of the injected current contributes to the current flow across the membrane in the form of ions, as the steady state ion fluxes re-equilibrate - this is called the IONIC CURRENT.
So the initial charging of the membrane capacitance causes a lag in the onset of the ionic current flow, which in turn is responsible for the lag in the change in membrane potential.
What is the time constant?
- The time constant is the time required to rise to approximately 63 % of the total change in potential.
- For most neurons, the time constant is between 1 –10 milliseconds.
Why is the time constant important?
- The rate at which the membrane changes in response to an individual stimulus and its subsequent relaxation determines how closely spaced sequential stimuli must be before there is summation of their effects.
- Longer time constant = greater summation of stimuli and possibility of reaching threshold upon repeated stimulation
What are cable properties?
• Most neurons have long processes or axons. They have many of the same electrical properties as an undersea cable. For this reason, the electrical characteristics involved in the spread of current and voltage changes along an axon are called CABLE PROPERTIES.
In the equivalent circuit, the axon is divided up into short segments or rings, and for each, there is the membrane resistance and capacitance for that segment, as well as a resistance to current flow through the inside of the axon, which is represented as ri.
In the equivalent circuit, the axon is divided up into short segments or rings, and for each, there is the membrane resistance and capacitance for that segment, as well as a resistance to current flow through the inside of the axon, which is represented as ri.
What is the length constant?
• The LENGTH CONSTANT (λ) is the distance (in centimeters) at which ~37% of the original change in membrane potential still occurs. A shorthand formula that is worth knowing is:
______
λ = √ (rm / ri) where
λ = the length constant (in centimeters)
rm = membrane resistance
ri = internal resistance to current flow
In most cells, the length constant is usually between 0.1 and 1.0 millimeters.
( about the distance in the nodes of ranvier)
What is the speed of propagation?
- membrane resistance (rm), membrane capacitance, (Cm) and the internal resistance to current flow (ri) affect the SPEED OF PROPAGATION is proportional to
1/ sqrt (Rm x Ri x Cm)
Consider:
rm ∝ 1/Diameter
ri ∝ 1/(Diameter)2
C ∝ Diameter
This means that AS THE AXON DIAMETER INCREASES (and the membrane resistance (rm) decreases, the capacitance (C ) increases, and the internal resistance to current flow (ri) decreases a great deal), THE SPEED OF PROPAGATION INCREASES. Thus, the squid giant axon has a high speed of propagation (which is a good thing for the squid….).
What is an action potential?
• a rapid depolarization and then repolarization of the membrane in response to a membrane depolarization of sufficient magnitude (not hyperpolarization).
Compare Na and K channels in response to depolarization.
• Na channels
o open in response to depolarization
o inactivates rapidly (despite maintained depolarization)
o needs repolarization before it can be active again
o depolarizes
• K channels
o Delayed opening in response to depolarization
o Does not inactivate
o Closes upon repolarization
o Repolarizes
o Note: there are many subtypes of K channels
• Delayed rectifying channels
• others
What is the threshold potential?
- The THRESHOLD is 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 ( INa > IK+ ILeak.)
- Na channel activation and inward current and thus a very rapid positive feedback cycle is begun.
- The depolarization also activates K channels, but they have a more sluggish response to depolarization and there is a lag before this conductance becomes appreciable, so it does not prevent this cycle from occurring.
Note: Na/Katpase does not play a role in action potential
The PROPORTION OF IONS THAT MOVE DURING AN ACTION POTENTIAL IS SMALL, and their intracellular concentrations will vary by less than one thousandth of the total.
Note: Na/Katpase does not play a role in action potential
The PROPORTION OF IONS THAT MOVE DURING AN ACTION POTENTIAL IS SMALL, and their intracellular concentrations will vary by less than one thousandth of the total.
Explain ion selectivity in an ion channel?
What aspects of an ion channels allow for selectivity?
• Size on Hydrated Ion: Na channel is not large enough for an K, but is large enough for an Li
o Hydrated radius of Na-H2O vs K-H2O
• Energy of hydration: K channel is large enough for dehydrated K, but not for hydrated Na.
o Since K is easier to dehydrate than Na, the channel pore loop pulls H2O off of K and allows K to pass through. The pore loop is not strong enough to dehydrate Na, so Na-H2O is too large to pass through.
• Note: the pore loops are what select for ions.
o Ex: if we change the amino acid structure of the pore loop, we can change an Na channel into a Ca channel
Explain the Voltage sensitivity of the channel
• S4 region senses voltage. Other aspects of the channel remain unchanged
o Has an unusual alpha helix
• Inside of the helix usu has only non-polar
• S4 has some charged amino acids which allows it to respond to voltage
• Arginine or lysine every third amino acid
o Differences in S4 regions between Na and K cause differences in speed of opening (Na fast, K slow)
o Areas of investigation: Paddle model vs helical twist model
Note: patch clamping allows f to measure the current of a single ion channel.
Note: patch clamping allows f to measure the current of a single ion channel.
Explain inactivation of ion channels. What are the differences between K and Na channels? What are the components?
• K channel inactivation
o Ball and chain on N terminus
• Has 4 ball and chains (only 1 ball needs to plug the channel)
o Ball is + charged
o When cytosol becomes thoroughly depolarized, the ball plugs the channel
• Na channel inactivation
o Small flap of + charged aminos
o When the cytosol becomes depolarized, the flap blocks the channel
• Note: there are 80 types of Na and K channels, not all inactivate
Explain the basic difference between T-type and L-type Ca channels?
Where are each located?
What is the length of opening?
• T-type
o Located at presynaptic terminals of nerve cells
o Open to release neurotransmitters
o Think “transient”
• L-type
o Found in cell membranes of the cell body
o Long-lasting
Explain the rate of opening of Ca channels compared to Na and K channels?
- Opening faster to slower: Na > Ca > K
* Closing faster to slower: Na > K > Ca
Remember the Ca plateau: Ca channels take longer to close than Na or K channels. How does norepi affect Ca plateau? What is the mechanism?
- shortens the duration of the action potential ie, the Ca plateau is shorter
- Norepi binds to G protein ==> βγ subunits binds to Ca channel and inhibits the channel ==> less Ca flows in and stays open shorter time
- Ex: this can be negative feedback. If norepi is released from neuron, it can inhibit the Ca channel of the same neuron
- Note: this occurs on Dorsal Root Ganglion nerves
What are delayed rectifier K channels?
Why are they slower to open than other K channels?
Why do they not inactivate?
- These K channels have one less + charged amino in their S4 region
- These K do not have a ball and chain to inactivate them
- Closed at resting membrane potentials and activated in response to membrane depolarization
- Their activation is usually slower than that for Na channels, and occurs with a slight lag
What is the IA current? What channel produces the IA current?
• The IA prolongs the depolarization of membrane, therefore increasing the length between repeated action potentials
• This is a K channel that causes the K current aka A current aka IA current
o These channels depolarize quickly compared to delayed rectifier K channels
• K flows out of these channels which attempts to hyperpolarize the cell. However, there are not enough to overcome the depolarization of the Na channels, so their only effect is to prolong the time of depolarization
What is the HCN channel? (Ih channel)
• Hyperpolarized and Cyclic Nucleotide-Gated channel
• They become activated at hyperpolarized states
• Influx of + ions, bringing the nerve from hyperpolarized back towards another threshold for a repeated action potential
• These channels are essential in pacemaker of rhythmically active cells
o Active area of study
How is the activity of HCN channels modulated?
• The activity of these channels is also modulated by cyclic nucleotides like cAMP
• HCN channels have a structure that resembles other voltage-gated channels
o 6 transmembrane regions in each subunit, pore loops, 4 subunits/channel
• Have an S4 region thought to undergo its shift in position in response to hyperpolarization.