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structure function of ion channels - Coggle Diagram
structure function of ion channels
barrier--mebrane
out of membrane molecules
hydrophobic molecules (O2, CO2
small uncharged polar molecules (H2O, ethanol
large uncharged polar molecules (glucose
ions (Na+, K+, etc
channels properties in the membrane
extracellular ligand
intracellular ligand
voltage
mechanical force
light
not gated (leaky conductance
gated ion channels
like K+ channel, cyclic nucleotide ion channels
composition
beta subunits
voltage sensor domain S1-S4) *4
alpha subunits
pore domain S5, 6) *4
subunits diversity
different genes for alpha subunits
e.g. hetromultimeric assembly of alpha subunits
different genes for auxiliary subunits (beta, gamma, delta)
e.g. Nav channel--cell type specific
alternative splicing of pre-mRNA of alpha subunits and auxiliary subunits
e.g. Cav channel
protein-protein interaction
cytoskeleton
epigenetics (e.g. phosphorylation
nomenclature
rNav1.1a
organism
r--rat
h--human
m--mouse
principle permeating ion
in this case: Na+
principle physiological regulator
v--voltage
ir--inward rectifier
gene subfamily/order of discovery
e.g. 1st 1 of 1.1
channel isoform/order of discovery
e.g. 2nd 1 of 1.1
splice variants
e.g. a of 1.1a
voltage gated
sodium channel
kinetics
activation
inactivation
resting
ion selectivity
recognized hydration shell
ion changes hydrogen bond network in water, water molecules reorient so that the polarized opposite charge concentration face ions
calcium channel
Ca2+ channels are only Ca2+ selective on presence of calcium. in calcium free solutions, they permeate other ions.
intracellular binding sites for Ca2+ and calmodulin trigger conformational changes that reduce Ca2+ influx
how to study conformational change
voltage clamp fluorometry
labal voltage sensor unit of the channel with fluorophore (cysteine-based labeling,
fluorophore close to membrane-> large F signal
ion channels activated -> fluorophore more in polar water -> smaller F signal
x-ray crystallography
by measuring angles and intensities of diffracted beams
substituted cysteine-accessibility
MTS reagents can covalently bind to accessible cysteine residues, thereby altering channel behaviors. Buried cysteine can not be modified
ligand-gated ion channels
structure
pentamers
cys-loop receptors
ACh/GABAa/glycine
tetramers
glutamate receptors
AMPA/kainate/NMDA
trimers
ATP receptors
P2X cation ion channel
Ach receptor
principle postsynaptic receptor of the neuromuscular junction in vertebrates
4 main subunits: 2 alpha, beta, gamma, delta
bind 2 ACh between alpha-delta and alpha-gamma to open the channel
the pore is lined by several ring sof negatively charged aa residues (gating ring
glutamate receptors
ionotropic
non-selective cation channels
AMPA, kainate
only permeate sodium and potassium
NMDA
light-gated
channelrhodopsin (naturally
absorb blue light max 480 nm
nonspecific channels
Hodgkin-Huxley model
sodium--depolarization
K--repolarization
conductance
single channel
ohm's law
multiple channels
ohm's law considering permeability
action potential
depolarization
repolarization
hyperpolarization (refractory period
resting
