Lecture 5: Ion Channels and Transporters pt.2 Flashcards
What are the 2 types of ligand-gated ion channels?
- neurotransmitter-gated ion channels
- cyclic nucleotide-gated ion channels
How do neurotransmitter-gated ion channels work?
The AMPA receptors have a clam-shell-shaped ligand binding domain, an extracellular ligand like glutamate binds to this domain and causes the clamshell structure to shut, this leads to the gate helices of the transmembrane domain to move, allowing the channel pore to open and the ion moves through
What are the 3 domains of the AMPA receptor?
amino-terminal domain, ligand-binding domain, and carboxyl-terminal domain
What do AMPA receptor antagonists do?
Block the channels
How do cyclic nucleotide-gated ion channels work?
Light triggers a pathway in these neurons that allows intracellular ligands like cyclic GMP to bind to the binding domain, the binding domain undergoes a conformational change that moves the linkers, thereby opening the channel gate and allowing cations to flow through the channel pore
What are the 4 subunits of a cyclic nucleotide-gated channel?
- pore-forming domain
- voltage sensor domain - sometimes affected
- linker
- cyclic-nucleotide binding domain
How do temperature-sensitive TRP channels work?
TRPV1 channel is gated by heat or capsaicin, they can open the channel pore by displacing membrane lipids closely associated with the helical linker that connects the sensor-like domains to the pore, causing a conformational change and opens the channel gates
What 2 gated channels is the structure of temperature-sensitive TRP channels similar to?
voltage-gated potassium and cyclic nucleotide-gated channels
What gated channel is the function of cyclic nucleotide-gate channels similar to?
voltage-gated potassium channel
true or false: TRP channels don’t have a selectivity filter and let cations flow through
true
How do mechanosensitive gated channels work?
Gated by mechanical displacement, members of the Piezo family are sensitive to touch and are extremely large with 38 transmembrane-spanning helices, they form a pore for cations and form 3 blades that act as levers for sensing membrane curvature, when mechanical force flattens the membrane, it flattens the curvature and this leads to tension building up which pushes the levers and the channel opens
What maintains the concentration gradient for all physiologically relevant ions?
active transport
What do active transporters require?
energy
What does the Na/K ATPase pump do?
maintains the gradient for Na and K
What does the Ca ATPase pump do?
prevents the intracellular [Ca] from accumulating
What are the 2 types of Ca ATPase pumps?
- PMCA
- SERCA
What does the PMCA do?
Responsible for extruding calcium from the cell of the neuron - pumps calcium out
What does SERCA do?
Responsible for removing calcium from the cytoplasm and pumping it into the sarcoplasmic reticulum
How does the Na/K ATPase pump work?
Using the hydrolysis of ATP, ATP binding promotes 3 Na removed and 2 K taken in, where pump phosphorylation promotes extracellular release of sodium and binding of potassium
What happened to the efflux of sodium when external potassium was removed?
Reduced efflux of sodium
What happened to the efflux of sodium when external potassium was returned?
Recovery of efflux of sodium
What happened to the efflux of sodium when ATP inhibitors were applied?
Reducing ATP synthesis has a significant decrease on the efflux of sodium
What happens to efflux of sodium when ATP synthesis is restored?
Recovery of sodium efflux
What is sodium efflux dependent on?
external potassium and ATP
Describe the translocation of Na and K by the Na pump
sodium binds, ATP phosphorylates the pump and leads to a conformation change and the efflux of sodium, allowing potassium to bind then dephosphorylations lead to another change in conformation (slightly different from the first conformational change), and potassium released
What do ion exchangers do?
Carry one or more ions up their electrochemical gradient, while simultaneously taking another ion down its gradient
What do ion exchangers use for energy?
Use the electrochemical gradient of other ions
What are the 2 types of ion exchangers?
- antiporters
- co-transporters
What are 2 examples of antiporters?
- Na/Ca exchanger
- Na/H exchanger
What do antiporters do?
exchange intracellular and extracellular ions
What does the Na/Ca exchanger help do?
keep intracellular [Ca] low
What does the Na/H exchanger help do?
regulates intracellular pH
What are 3 examples of a co-transporter?
- Na/K/Cl co-transporter
- K/Cl co-transporter
- Na/neurotransmitter co-transporter
What do co-transporters do?
carry multiple ions in the same direction
What does the Na/K/Cl co-transporter help do?
regulates intracellular [Cl]
Which ion’s gradient do antiporters use to function?
sodium
Describe the function of the Na/Ca exchanger
binding of cytoplasmic Ca causes the gating bundle to slide across the core helices, changing the conformation to face outward, then the outward-facing conformation releases Ca outside the cell, next the inward-facing conformation releases Na into the cytoplasm and the outward-facing conformation binds Na, causing the gating bundle to slide back to restore the inward-facing conformation
