Transport in Membranes: Ionophores, Porins, Channels, Aquaporins, Schemes and Mind Maps of Thermodynamics

Download Transport in Membranes: Ionophores, Porins, Channels, Aquaporins and more Schemes and Mind Maps Thermodynamics in PDF only on Docsity!

Passive and Active Transport

1. Thermodynamics of **transport

2. Passive-mediated** **transport
3. Active transport** neuron, membrane potential, ion transport

Membranes

• Provide barrier function
  • Extracellular
  • Organelles
• Barrier can be overcome by „transport proteins“
  • To mediate transmembrane movements of ions, Na
    • , K +
  • Nutrients, glucose, amino acids etc.
  • Water (aquaporins)

Two types of transport across a membrane: o Nonmediated transport occurs by passive diffusion, i.e., O 2

, CO

2

driven by chemical potential gradient, i.e.

cannot occur against a concentration gradient

o Mediated transport occurs by dedicated transport proteins

1. Passive-mediated transport/facilitated diffusion : [high] -> [low]

2. Active transport : [low] -> [high] May require energy in form of ATP or in form of a membrane potential

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

Valinomycin

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)

B) Porins

o Membrane spanning proteins with β-barrel structure, with central aqueous channel, diameter ~ 7x11Å ~600 D, little substrate

selectivity, E. coli OmpF

o Maltoporin , substrate selectivity for maltodextrins, α(1->4)- linked glucose oligossaccharide degradation products of

starch, greasy slide

C) Ion Channels

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

The selectivity filter

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

Ion channels are gated

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

V

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