Sodium Channels Flashcards
Name the six main types of ion channels.
Voltage-gated.
Ligand-gated.
Mechanically-gated.
Temperature-gated.
G-protein-gated.
Phosphorylation-gated.
Define gating.
The process of opening and closing the gates of an ion channel in response to external signals.
What is an active channel?
A channel that has gates that can open or close the channel.
What is a passive channel?
A channel that is always open, so ions can pass through continuously.
Name a specific passive channel that contributes to neuron’s RMP.
KCNK 2-pore potassium channel.
A change in voltage across the membrane activates voltage-gated sodium channels, and sodium rushes into the neuron. Why is this inward current only transient?
Voltage-gated sodium channels inactivate despite continued depolarisation of the membrane potential.
Which voltage-gated sodium channels contribute to the rising phase of an AP?
Nav1.6.
Nav1.7.
Nav1.8.
Which voltage-gated sodium channels contribute to the amplification of subthreshold stimuli of an AP?
Nav1.3.
Nav1.7.
Nav1.9.
Describe the basic structure of the voltage-gated sodium channel.
Large multimeric complex.
Alpha subunit and one or more smaller auxiliary beta subunits.
Where is the ion-conducting aqueous pore found in a voltage-gated sodium channel?
Within the alpha subunit.
What is the role of the auxiliary beta subunits in a voltage-gated sodium channel?
Modify the kinetics and voltage-dependence of the gating.
How is an Nav a tetramer-mimicking structure?
It looks like it’s composed of multiple subunits but it’s actually a single polypeptide chain folded into a 3D structure (monomer of around 2000 amino acids).
Describe the domains of an Nav.
DI-DIV.
Each domain consists of 6 transmembrane spanning alpha helices (S1-S6).
Which helices make up the voltage-sensing domain (VSD) of an Nav?
S1-S4.
Which helices make up part of the pore domain (PD) of an Nav?
S5 and S6.
A sequence of amino acids that connect domains III and IV of an Nav make up what?
The portion of the channel responsible for inactivation.
Why is it important to identify regions of a gene or protein that have been conserved over time?
It is an important clue regarding the parts of a gene or protein that are most important.
What is the function of the arginine repeats on S4 of an Nav?
It is a key evolutionary feature that ensures that the arginine residues align at the same point on each bend in the coil of S4, forming a positively-charged band along the length of the alpha helix.
What is the characteristic and conserved pattern in the location of arginine residues on S4 of an Nav?
Arginine repeats every 3 amino acids.
Describe the sliding helix model of channel activation.
S4 is pulled inwards when the neuron is at rest.
It is repelled outwards when the membrane is depolarised.
How are S4 and S5 connected to each other?
Via a sequence known as a linker.
How does the physical movement of S4 when it is repelled due to depolarisation lead to a change in conformation of the Nav?
The physical movement of S4 pulls on the S4-S5 linker and shifts the position of S5 and S6.
Why is the S4-S5 linker essential for electromechanical coupling between the voltage sensor and the pore domain?
It physically connects the voltage sensor to the pore domain.
How is the selectivity filter of an Nav formed?
Four key residues form the selectivity filter.
They are an aspartate-glutamate-lysine-alanine (DEKA) motif.
Each domain contributes an amino acid to this motif.
