Blake_Biochem_19_Transport through membranes II Flashcards
Ion Channels (6)
- Integral, polytopic membrane proteins
- Mediate facilitated passive transport (enzyme-like)
- 1000x faster than pumps
- highly selective and specific (esp Na+, K+, Ca++)
- Respond to physical and chemical changes with precisely timed conformational changes
- Opening and closing of channels shape the membrane potential
Types of Ion Channels
- Voltage-gated (Na+, Ca++, K+)
- Chemically gated (Ach receptors)
- Mechanically gated (sensory neurons)
How are cell membrane currents measured?
Patchclamping
Sodium channels are highly homologous to what other channels?
Calcium channels
What is the putative model of a Sodium channel (or potasium channel)?
- 4 groups of 6 Transmembrane domains
- S1-4 voltage sensor
- S5-6 pore
tedrodotoxin
- Found in puffer fish
- blocks Sodium channels => prohibits ion flow
- causes permanent damage unlike pharmeceutical anesthetics which use a similar but temporary mechanism
How were sodium channels isolated?
purified from electric eel
how were potasium channels isolated?
not purified from natural source. Instead, genome was sequenced and chystalographyic structure was proposed.
A researcher mutated a critical domain on the Na+/K+ - ATPase gene. When expressed in cells, the mutated protein was unable to form the EP intermediate in the reaction cycle of the enzyme. Which amino acid was most likely altered in the mutant protein?
Aspartate
A 60 year old man arrived to the Emergency Room complaining of chest pain, shortness of breath and swelling of the legs. Echocardiography results showed evidence of congestive heart failure. The attending physician immediately started him on Digitalis. Which ion transporter/channel is the primary target of this drug?
Sodium Potassium ATPase
Explain the mechanism of K+ selectivity filter
- TVGYG signature
- forms carbonyl bonds with K+ ions dehydrating the encapsulated ion
- 4 sites for K+ binding cause repulsion of like charges so K+ is expelled
- Resolvation of K+ channel is energetically favorable
Why are Na+ ions not exported through the K+ selectivity filter?
Resolvation of Na+ is not energetically favorable (ie: the magnitude of the energy of desolvation is greater than the magnitude of the energy of resolvation)
Model of Voltage Gating
How are Sodium and potassium channels gated?
- They are gated by membrane potential.
- Sensors (S1-4) trigger conformational changes which open and close the channel.
- Inactivation is accomplished with a “ball-and-chain” like mechanism which mechanically plugs the pore when depolarization becomes too rapid.
Acetylcholine receptor:
General Function
- Ligand gated by Ach
- Post synaptic side of synaptic cleft
- Bindingof Ach opens the channel
- Channel is permeable to Na+ and K+
Acetylcholine receptor:
Structure
- Pentamer fof 4 kinds of membrane spanning subunits (2alphas, 1Beta, 1gamma, 1delta) arranged in the form of a ring that creates a pore through the membrane.
- Each subunit contains extracellular, membrane-spanning, and intracellular domains