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An in-depth exploration of passive and active transport across membranes, focusing on ionophores, porins, ion channels, and aquaporins. It covers the thermodynamics of transport, passive-mediated transport, and active transport, as well as specific examples of ionophores, porins, and ion channels. The document also discusses the role of these transport mechanisms in maintaining osmotic balance, signal transduction, and membrane potential.
What you will learn
Typology: Schemes and Mind Maps
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1. Thermodynamics of **transport
Two types of transport across a membrane: o Nonmediated transport occurs by passive diffusion, i.e., O 2
2
o Mediated transport occurs by dedicated transport proteins
1. Passive-mediated transport/facilitated diffusion : [high] -> [low]
A) Ionophores Organic molecules of divers types, often of bacterial origin => Increase the permeability of a target membrane for ions, frequently antibiotic, result in collapse of target membrane potential by ion equilibration
1. Carrier Ionophore , make ion soluble in membrane, i.e. valinomycin, 10 4 K + /sec 2. Cannel-forming ionophores , form transmembrane channels, gramicidin A, 10 7 K + /sec
o One of the best characterized ionophores, binds K
ions o Cyclic peptide with D- and L-Aa o Discrimination between Na
, K
, Li
? K
(r=1.33Å), Na
(r=0.95Å)
o Membrane spanning proteins with β-barrel structure, with central aqueous channel, diameter ~ 7x11Å ~600 D, little substrate
o Maltoporin , substrate selectivity for maltodextrins, α(1->4)- linked glucose oligossaccharide degradation products of
o All organisms have channels for Na
, K
, and Cl
o Membrane transport of these ions is important for: o Osmotic balance o Signal transduction o Membrane potential o Mammalian cells: extracellular: 150mM Na
, 4mM K
intracellular: 12mM Na
, 140mM K
passive diffusion of K
ions through opening of **K
channels** from cytosol to extracellular space **K
-channels** have high selectivity of K
over Na
selectivity 10 4
o The ion needs to be dehydrated to pass through the most narrow opening of the channel o In the dehydration, water is replaced by hydroxyl groups from the channels amino acids o These hydroxyls will stabilize K
but not Na
, because Na
is much smaller than K
o Cavity in the middle of the channel = middle of the membrane !!! Contains water
o Channels can be closed and opened upon signal: o Mechanosensitive channels open in response to membrane deformation: touch, sound, osmotic pressure o Ligand-gated channels open in response to extracellular chemical stimulus: neurotransmission o Signal-gated channel, open for example on intracellular binding of Ca 2+ o Voltage-gated channel: open in response to membrane potential change, transmission of nerve impulses
Time course of an action potential
Voltage gated K
channels o Tetramer, S5,S6 ~KcsA, T1 domain in cytosol o Gating by the motion of a protein paddle o S4 helix contains 5 positive charges, spaced by 3 Aa = acts as voltage sensor
Ion channels have two gates o One to open and one to close o T1 domain contains inactivation peptide that blocks pore entrance a few ms after V-dependent pore opening
Cl
- channel differ from cation channels o Present in all cell types. Permit transmembrane movement of chloride ions along concentration gradient: [Cl
] extracellular: 120mM; intracellular 4mM o Homodimer with each 18TMDs