Evolutionary History of Ion Channels and

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Evolutionary History of Ion Channels
and Neurotransmitters
Neuro Journal Club, 06.03.08 Peter HANTZ, Arendt
Laboratory
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Types of Ion Channels
Voltage, and voltage/intracellular ligand-gated
ion channles K VG fastly and slowly
activated, inward rectifier,
leak-channels V/ILG Ca-activated,
ATP-activated, cyclic-nucleotide gated
Ca VG High voltage activated, Low voltage
activated V/ILG Ca-activated, IP3 activated
Na, Cl-, H mostly VG
Stretch-activated ion channels Large-conductance
MSc Low-conductance MSc Light-gated ion
channels
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Types of Ion Channels/Receptors
Neurotransmitter systems Ionotropic receptors
(ligand-gated ion channels) Cys-loop receptors
"fast activating" Anionic(inhibitory) Gly,
GABA Cationic(excitatory) 5HT, Ach
(nicotinic) Glutamate Gated Channels Glutamate
, agonists AMPA, NMDA, kainate G-protein
coupled (metabotropic) receptors ACh, Glu
(AMPA, KAIN, NMDA), GABA, 5-HT, DA, NE,
... Shortcut pathway, Second Messenger
Cascade Other neurotransmitter
receptors peptides, NO, CO
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Precursors of the VG-like ion channels
small synthetic peptides -fold into
a-helixes -voltage inserted into
membranes -spontaneously build ion 5-7 mer
channels 1-TM ion channels Influenza M2
tetramer 2-TM ion channels simplest K
channels KcsA, Kir (inwardly rectifier)
tetramer Present in all three domains of life No
voltage-sensitivity
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Voltage-sensitive Potassium Channels
Gene fusion/duplication 1.-4. subunits
containing six transmembrane crossings S1-S4
voltage gating S4 charged voltage sensor S5,
S6 conserved selectivity filter KvAP
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6TM-type channels
Voltage and cyclic nucleotide-gated
channels one-domain, 6TM homotetramers
Usual structure of Na and Ca channels a1
subunits four LINKED DOMAINS Each six
transmembrane elements
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Possible origins of the 6TM channels
Two rounds of gene duplications? -Similarities
domains I and III domains II and
IV -Two-domain channels were identified
(TPC) They evolved from one-domain 6TM
multimers? Ca or Na-channels are more
ancestral? 4-domain Ca-channel already in
yeast 4-domain Na-channel only in multicellular
animals not detected in protozoa, in plants
But There is an ancestral bacterial 6TM
homotetrameric Na-channel Note two types of
"inactivation" mechanisms (following
activation) "ball and chain" or "inactivation
loop" Cl channels conservative, structurally
distinct (10-12 domains)
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Evolution of the LG-like ion channels
Structure (Cys-loop "fast activating"
channels) Mostly pentamers of 1-domain 4-TM
proteins N-term extracellular domain ligand
binding site Made of several unrelated
proteins? Homologs in bacteria Ancient role
nutrient seeking? osmotic regulation? Now
intercellular communication
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Evolution of the LG-like ion channels
Ancient ACh, 5HT and GABA Gly derived from
GABA despite Gly is "more simple" Root?
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Structure of the GPCR
Single, 7TM polypeptide 2 extracellular loops
transmitter binding site 2 intracellular loops
activate G-proteins Two major
groups PLC-activating (IP3) cAMP decrease Ev.
connection between ionotropic (LGICh) and
metabotropic (GPCR) receptors ?
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Evolution of the GPCR
7-TM architecture in procaryotes bacteriorhodopsi
ns, no GPC ...linkage to eucaryotic GPCR ?
(disputed) GPCR Present in plants, fungi and
animals common ancestor, 1.2 Gy ago
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