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67 Cards in this Set
- Front
- Back
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What does the conductance of the membrane to ions do during the action potential?
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Increase
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Why is voltage-clamp necessary to study the action potential? |
The postive feedback once threshold is achieved makes it impossible to study at a particular voltage |
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What is the basic function of the voltage clamp?
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To interrupt the interaction between the opening and closing of voltage-gated channels and membrane potential
To prevent the changes in membrane current from influencing the membrane potential |
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How do you obtain the membrane current with voltage clamp? |
By recording the current that must be generated by the voltage clamp to keep the membrane potential from changing |
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What is the relationship between the membrane voltage and the charge on the membrane capacitance? |
They are proportional |
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How can the capacitive current be separated from the ion currents? |
It is immediate and instantaneous |
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Do the voltage-gated sodium channels have different or the same kinetics? |
Different |
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Describe the ionic current during a voltage step. |
A small, steady outward current that persists for the duration of the pulse |
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Describe the capacitive current during a voltage step. |
There is a very brief outward instantaneous current that discharges the membrane capacitance; at the end of the step there is a brief inward capacitance current as the ionic current goes to zero |
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What is leakage current, Il? |
The current that flows through the nongated channels of the membrane |
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What current is responsible for generating the resting potential? |
Leakage current |
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What is the simple interpretation of the findings of a switch from inward current to outward current for large depolarization pulses? |
The depolarizing voltage step sequentially turns on active conductance channels for two separate ions: one for inward current and another for outward current |
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How do you block voltage-gated Na+ channels? |
Tetrodotoxin |
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How do you block voltage-gated K+ channels? |
Tetraethylammonium |
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How do you measure leakage current?
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It doesn't vary with Vm or time, it is constant so it is readily subtracted
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How do you measure ionic current? |
Leakage current is readily subtracted from Im, as is the capacitive current because it occurs only briefly at the beginning and end of the pulse |
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How do you measure the ionic current for one ion? |
Block the other ion using either TTX or TEA and eliminate leakage and capacitance currents |
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Which current's membrane potential is the resting potential equivalent to? |
Leakage potential |
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What are the similarities in the kinetics of Na+ and K+ voltage-gated channels? |
Open in response to depolarizing steps of membrane potential Do so more rapidly and to a greater extent for alrger depolarizations |
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How do Na+ and K+ voltage-gated channels differ? |
Na+ channels open more rapidly, close more rapidly when the pulse is brief, when the pulse is maintained, Na+ begin to close, or inactivate, while K+ channels remain open for the duration of the depolarization |
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What are the three states a Na+ channel can exist in? |
Resting, activated, or inactivated |
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What happens to the state of the Na+ channel upon initial depolarization? |
Goes from resting (closed) to activated (open) |
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If the depolarization is brief, what happens to the state of the Na+ channel? |
It goes from closed to open back to closed |
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If the depolarization is maintained, what happens to the state of the Na+ channel? |
The channel goes from closed to open to inactivated to briefly open to closed |
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Describe the inactivated state of the Na+ channel. |
It cannot be activated (opened) by depolarization |
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How can inactivation be changed to closed? |
Only by repolarizing the membrane |
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What is the activation gate? |
It is closed rapidly when the membrane is at its resting potential and is rapidly activated by depolarization |
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What is the inactivation gate? |
It is open at the resting potential and closes slowly in response to depolarization |
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What is the sequence of events in the Hodgkin-Huxley model of the action potential? |
1) A depolarization fo the membrane causes a rapid opening of Na+ channels (an increase in gNa) 2) This results in an inward Na+ current 3) This current, by discharging the membrane capacitance, causes further depolarization 4) More Na+ channels open 5) This regenerative process generates an action potential |
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What two factors limit the duration of the action potential? |
1) The depolarization of the action potential gradually inactivates the Na+ channels 2) The depolarization opens, with some delay, the voltage-gated K+ channels, increasing gK |
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What is the hyperpolarizing afterpotential? |
A transient hyperpolarization following the action potential because K+ channels close some time after Vm has returned to its resting value |
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What are the two phases of refractoriness? |
Absolute refractory period Relative refractory period |
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Describe the absolute refractory period. |
It comes immediately after the action potential; it is impossible to excite the cell |
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Describe the relative refractory period. |
Directly follows the absolute refractory period; it is possible to trigger an action potential, but only by applying stimuli that are stronger than normal |
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What causes the periods of refractoriness? |
The residual inactivation of Na+ channels and opening of K+ channels |
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What are two outward currents that are increased by a small subthreshold depolarization? |
Ik and Il |
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Why is there a threshold for the action potential? |
Because Ik and Il oppose the depolarization action of Na+ influx and it takes a certain voltage for the Na+ influx to overcome the resisting currents |
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What defines the threshold for the action potential? |
The value of Vm at which the net ionic current (INa+IK+Il) just changes from outward to inward, depositing positive charge on the inside of the membrane |
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What are five fundamental conclusions from testing the Hodgkin-Huxley model? |
1) The basic mechanism of action potentials is the same in all neurons 2) The nervous system expresses a rich variety of voltage-gated ion channels 3) Gating of voltage-sensitive ion channels can be influenced by changes in intracellular ion concentrations 4) Excitability properties vary among neurons 5) Excitability properties vary within regions of the neuron |
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Which channels do most neurons have? |
Na+ and K+ channels, as well as voltage-gated Ca2+ channels, some also have voltage-gated Cl- channels |
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Can Ca2+ channels contribute to the upward stroke of the action potential?
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Yes
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How do the different channels of the same ion differ? |
Kinetics of activation, voltage activation range, and sensitivity to various ligands |
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What are the four common variants of the K+ channel? |
1) The delayed rectifier: slowly activated channel described by H and H 2) The Ca2+-activated K+ channel: activated by depolarization but voltage sensitivity is a function of intracellular Ca2+ concentration 3) The fast, transient (A-type) K+ channel: activated rapidly by depolarization, inactivates rapidly but only if depolarization is maintained 4) M-type channel: activated by depolarization but inactivated by Ach |
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How many types of voltage-gated Ca2+ channels are there? |
At least 3 |
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How many types of voltage-gated sodium channels are there? |
At least 2 |
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Which ion's concentration has the greatest modulatory effect on the cell? |
Ca2+ |
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What is an example of a modulatory effect of Ca2+ influx?
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It can activate a Ca2+ sensitive protein phosphatase, calcineurin, which dephosphorylates the channel, inactivating it
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How can Ca2+ influx be self-limiting? |
Opens Ca2+-activated K+ channels and closes Ca2+ channels |
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What are the different ways cells can respond to constant excitatory input? |
Decelerating train of spikes Accelerating train Constant firing frequency |
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Which parts of the cell have a greater variety of channels? |
Dendrites, cell body, axon hillock, and nerve terminals |
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How would you determine the density of voltage-gated Na+ channels? |
Radiolabeled tetrodotoxin |
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What is the relationship between the density of Na+ channels to the conduction velocity of the action potential? |
Direct |
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Why can't you measure the current flow through a single channel in voltage-clamp experiments? |
1) The voltage calmp surveys a large area in which thousands fo channels are opening and closing randomly 2) Background noise is much larger than the current flow through any one channel |
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What varies and what remains constant in the opening of a single channel? |
The duration it remains open is variable but the amplitude of the current remains the same |
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What is gating charge? |
Postulated by H and H to explain gating molecule state change; the gating molecule's net charge |
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What is gating current? |
A small extra component of outward capacitive current necessary to keep the membrane potential constant to allow for the energy required to change the gating conformation; Ig |
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What are two important properties of the Na+ channel provided by studying the gating current? |
1) Gating is a multistep process 2) Activation and inactivation are coupled processes |
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Can the activation gate close while the channel is inactivated? |
No |
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What mechanism causes the inactivation of A-type K+ channels? |
A ball-and-chain mechanism |
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What determines the ion selectivity of a channel? |
Size and charge; degree of effectiveness of the carboxylic groups for replacing the waters of hydration changes with different ion species |
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Which subunit forms the aqueous pore of the voltage-gated Na+ channel? |
Alpha |
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What role do the beta subunits play in the Na+ channel? |
Structural, stabilizing, or regulatory |
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What are two fundamental structural features of the Na+ channel?
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1) The ion-containing portion of the sodium channel has four internal repetitions
2) The S4 region |
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Describe the S4 region of the voltage-gated Na+ channel. |
Highly conserved and is homologous to regions of voltage-gated K+ and Ca2+ channels May transduce charge and open the activation gate High density of charged amino acid residues; every third aa has a net positive charge Forms an alpha helix |
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What forms the K+ channel? |
4 subunits that aggregate around a central pore |
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What three major technical advances have led to explanations of the mechanisms of action of voltage-gated channels?
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1) Voltage-clamp extended to patch-clamp recording and gating-current analysis
2) Isolation of neurotoxins made it possible to estimate the density of the Na+ channels, purify Na+ and Ca2+ channels, and determine their sequences by sequencing cDNA clones 3) Combined genetic and molecular biological approach has led to the sequence for K+ channels |
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What is the voltage clamp? |
A current source connected to two electrodes, one inside and the other outside the cell |
