Ion channels Flashcards
Outline the basic structure of a voltage gated sodium channel.
Which part of the structure makes up the voltage sensor? What is its significance?
The P loop acts as a _X__ to keep large ions out of the cell. No matter which channel you’re talking about, you need __ P loops to make a complete X. The X function of the P loop specifically comes from the sequential of __-__-__ residues, whose carbonyl O’s point inwards which allows
S4 domains contain positively charged component (lysine/arginine residue @ every 3rd position) that detects changes in membrane potential
Selectivity filter. 4 P loops needed for a complete selectivity filter
What are the types of K+ channels discussed (in the Ion channel lecture and in general)?
(for the Ion channel lecture)
Voltage gated K+ channel
Inward rectifier K+ channel
2 pore domain K+ channel
(in general)
BKca channels (Ca2+ sensitive K+ channels)
HERG channels
A-type K+ channels
ATP-sensitive K+ channels
True/False: The voltage gated K+ channel is exactly like the voltage gated Na+ channel.
How is the inward rectifier channel different from the voltage gated K+ channel?
The selectivity filter function of the P loop specifically comes from the sequential of __-__-__ residues, whose carbonyl O’s point inwards
False. The voltage gated K+ channel has 4 individual subunits (that link together?) that form the channel
The inward rectifier channel typically allows for inward flow of current whereas the Voltage Gated K+ channel typically allows for outward potassium current. It does still need 4 individual subunits to form functional channel.
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An action potential is initiated by injecting current into an axon. Describe the sequence of events that occurs at the site of initiation of the action potential. Include the role of voltage-gated Na+ channels, voltage-gated K+ channels, INa, IK, IC (capacitive current) and Na+ channel inactivation.
For a membrane that is permeable only to K+, draw an electrical circuit that shows the equivalent of the K+ channel, K+ concentration gradient and capacitance
Define current (in words and mathematically)
What is the sign convention for flux of anions vs flux of cations?
Define resistance and conductance. Describe the relationship between resistance and conductance.
Movement of (positive charge) per unit time
I = q/t
Flux for anions: opposite direction from current flow
Flux for cations: same direction as current flow
Resistance and current have an inverse relationship
Using the diagram below, describe the microelectrode experiment used to explain the linear relationship between voltage and current.
Define reversal potential
Microelectrodes: intracellular positive charge moves away from the membrane, which causes the memb to become more negative, thus an inward current hyperpolarizes the membrane
Change in Vm is delayed in response to step change in current
Reversal potential = Vm at which current changes direction
Describe Ohm’s law with respect to conductance. How do you calculate conductance and what is the significance of ion channel open probability?
How do you find the current flowing through a single channel? Contrast that macroscopic current.
Describe the significance of capacitance. How do you calculate it and what is it’s relationship to the distance between plates/distance through which charge is flowing?
Capacitance = ability to separate charge across a membrane or store it
Assuming you had a parallel plate conductor, draw and describe the significance of capacitive current and describe the difference between capacitive and ionic current
What are the changes to the membrane potential if the capacitive current is outward? Inwards?
Capacitive current results in charge separation between the two plates, even though there is no ion flow between them
Capacitive current: current that induces a change in membrane potential; Ionic current: current induced by flow of ions across membrane
Ic = +ve (outward) >> depolarizing
Ic = -ve (inward) >> hyperpolarizing
Using the diagram below, describe the flow of current in the current clamp experiment.
Where does the current flow first? Why? What is the factor that then allows for ionic current to start flowing? Which current is contributing to changes in Vm by the end of the experiment?
What is the significance of the membrane time constant? How do you calculate it and what is its effect on the rate of change of Vm/conduction velocity of an action potential?
Membrane time constant = how long it takes for Vm to change
Tm = Rm X Cm, where Rm is the resistance when all the channels are open (i.e. at steady state) and Cm = capacitance
Describe the significance of the length constant. How do you calculate it and what is the effect of a longer/shorter length constant on the conduction velocity of an action potential?
Length constant is a ratio of the membrane and internal resistance (of an axon); tells you how well current is going to flow down the length of an axon
If Rm = high, more current will be passed down the length of the axon
In Ri = high, less current will be passed down the axon coz it leaks out
Thus, a longer length constant = faster conduction velocity of an action potential
What is the difference between the absolute and relative refractory periods? Which channels/gates are involved in either period?
Absolute refractory period: period of time during which an action potential absolutely can’t be initiated
Relative refractory period: interval immediately after absolute refractory period during which action potential is inhibited but not impossible
What are the types of voltage gated Ca2+ channels and how do they operate?
L type Ca2+ channels
P type Ca2+ channels
In general, Ca2+ channels activate slowly, thus in AP, they have a slower upstroke (accounts for “slow response” myocardial AP in SA/AV nodal cells)
Draw a curve showing an AP in ventricular cardiac muscle. Describe the various phases of the AP. Which channels are open/closed at each stage (What is the role of voltage gated Ca2+ channels)?
What are the types of voltage gated K+ channels discussed and what are the characteristics of each?
A Type K+ channels -have activation and inactivation gates (biphasic)
BKca channels (aka Calcium dependent K+ channels) - opened by increasing intracellular Ca2+ concentration/depolarizing Vm
ATP sensitive K+ channel - low intracellular ATP in pancreatic beta cells = K+ efflux (hyperpolarization); blockage = Vm depolarization
HERG channels: responsible for repolarization in cardiac AP
What is the effect of Sulfonylureas on ATP sensitive K+ channels?
Sulfonylureas block Surl-TrpM4 K+ channel, which causes depolarization of the membrane and allows for AP generation. Used to treat Type 2 diabetes, but not anymore due to pts developing hypoglycemia
Describe the role of HERG K+ channels in the generation of cardiac action potential and the effects of mutations in the HERG channels
HERG K+ channels generate the AP in the QT interval (marks ventricular action potential)
Mutations result in Long QT syndrome
