Blake_Biochem_19_Transport through membranes II Flashcards
(28 cards)
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
Neurotransmission (4 facts)
- Most important manifestation of membrane transport - basis for communication in the nervous system
- Nerve impulse is an electrical signal produced by the flow of current across the plasma membrane of a neuron
- Inside of Nuron has HIGH K+ and LOW Na+
- Gradient is generated by Na+/K+ ATPase
Nernst Equation
Veq= -(2.303) (RT/zF) log10([Cin]/[Cout])
Action Potential (4facts)
- AP arises from large transient changes in the permeability of axial membrane ions
- The conductance for Na+ changes first due to opening of Na+ channels
- Depolarization increases permeability to Na+ which begin to flow in via Na+ Channel due to high concentration outiside
- Depolarization then opens K+channels and K+ move out
Label the numbers
Which Ion channels are closed more slowly: Sodium or Potassium?
Potassium
Gap Junctions (4) (+7 steps in AP)
- Special form of Ion Channels
- “cell to cell” channels
- Passages btwn contiguous cells
- Important role in cell to cell communication
Structual Features of Gap Junctions
- Packed in Hexagonal array
- Lumen (~20Å)
- Distance btwn gap jx of adjacent cells ~35Å
Properties of Gap Junctions
- Small Hydrophillic molecules and ions can pass through
- Lest than 1kDa molecules can pass through (eg: sugars, amino acids, and nucleotides)
- Proteins, polysaccharides, and nucleic acids cannot pass through
Structure of Gap Junctions
- Each channel is made of 12 molecules of CONNEXIN
- SIX connexin molecules are hexagonally arrayed to form a half channel called a “connexon”
- Two connexons join end-to-end in the intercellular space to form a functional channel
