Potassium Channels Flashcards
(40 cards)
Name the four families of potassium channels.
Voltage-gated (Kv).
Calcium-activated (Kca).
Inwardly-rectifying (Kir).
Two-pore (K2P).
What are the four similarities between all four families of potassium channels?
Highly conserved selectivity filter within the pore.
Same tetrameric architecture with a single pore.
Enable potassium ions to flow across membrane.
Essential in controlling neuronal excitability.
Describe the structure of inwardly-rectifying potassium channels (Kir).
Each subunit is formed of two transmembrane domains separated by a pore-forming region.
Subunits form tetramers.
Kir channels show strong inward rectification. What does this mean?
Potassium ions move more easily into the cell than out.
When are Kir channels activated and inactivated?
Activated around the equilibrium concentration for potassium (Ek), so helps to set and maintain the RMP.
Inactivated when membrane is depolarised to avoid opposing membrane excitation.
Describe the structure of two-pore potassium channels.
Four transmembrane domains.
Two pore domains per subunit.
What type of conductance do two-pore potassium channels contribute to?
“Leak” potassium conductance.
Name six stimuli that regulate two-pore potassium channels.
pH.
O2 partial pressure.
Membrane stretch.
Temperature.
G-proteins.
Fatty acids.
Describe the structure of calcium-activated potassium channels.
Share a similar structure to voltage-gated potassium channels.
Possess an extra transmembrane domain, named S0, that is involved in regulation by beta subunits.
What regulates calcium-activated potassium channels?
Voltage.
Intracellular calcium.
Describe the structure of voltage-gated potassium channels (Kv).
Six transmembrane domains per subunit.
Voltage sensor on S4.
Four alpha subunits form the pore region.
Alpha subunits associate with auxiliary beta subunits.
What is the role of Kv channels?
Repolarise membranes in neurons and muscle cells.
Control AP frequency and duration.
Why is potassium forced out of a neuron when Kv channels are activated?
High concentration of potassium inside the neuron.
Large ionic driving forces acting on neuron.
Kv channels consist primarily of four identical alpha subunits. What is the name for this structure?
Homotetramer.
What constitutes the main voltage-sensing region in Kv channels?
5 conserved arginine residues on S4 that repeat every 3 amino acid sequences.
Describe the sliding helix model of Kv gating.
Charged S4 segments move across the membrane - similar to a peg in a hole.
Describe the paddle model of Kv gating.
The gating charge is carried by paddles, composed of an alpha-helical hairpin formed by S3 and S4, on the outside of the channel that pivot against the membrane like levers, directly causing channel activation.
Describe the transporter-like model of Kv gating.
The charged residues on S4 pivot along their longitudinal axis, transporting the gating charge from an extracellularly to an intracellularly connected water crevice, and coupling to the opening and closing of the ion channel.
What is the role of the selectivity filter?
Allows passage of potassium ions that have shed their hydration shell.
What is the BC gate?
The bundle crossing of the M2/S6 helices.
What is the role of the BC gate?
Forms a barrier for hydrated potassium ions.
How is the selectivity filter highly conserved?
The P-loop that forms the channel’s selectivity filter contains the TVGYGD signature sequence.
There is a highly conserved glycine residue in the middle of the inner pore helix.
Why can the selectivity process be thought of as a series of stereochemical checkpoints?
The main constituents of the filter are oxygen atoms from amino-acid residues Thr-Val-Gly-Tyr-Gly. Each checkpoint consists of four oxygen atoms that occupy the corners of a square.
The narrow size of the pore is thought to do what?
Strip potassium ions of their hydration shell as they enter the channel.
