voltage gated ion channels Flashcards
examples of voltage gated channels
na+ channels
k+ channels
h+ channels
cl- channels
ca2+ channels
why study voltage gated sodium and potassium channels?
na+ channels are responsible for the depolarisation phase
k+ channels are responsible for the repolarisation phase
different k+ channels are responsible for different phases of the
repolarisation and after hyperpolarisation
why study voltage gated calcium channels?
ca2+ channels are required for transmitter release during neurotransmission
ca2+ channels can also be found on dendrites and soma
increase in calcium leads to increase in calcium activated channels in endoplasmic reticulum from intracellular store
what is a VGIC?
an ion channel that opens in response to a change in the membrane potential
basic structure of VGIC
made up of two domains: voltage sensing domain (hydrophobic) and pore domain (hydrophillic)
ion cannot pass through PLB
forms tetrameric structure with four domains (alpha helical)
voltage sensing domain on the outside
voltage gated potassium channel structure
subunits consist of 6 transmembrane domains
all alpha helices
S5 and S6 form the pore domain
S1-S4 forms the voltage sensing domain
S4= primary voltage sensor. +ve AA (e.g arginine) which has conformational change following depolarisation=opens gate
P-LOOP forms the ion selecitivty filter (S5-S6) which allows only potassium
what are inward rectifying channels (kir)?
are a type of ion channel that allow ions to flow more easily into the cell (inward current) than out of the cell (outward current), a phenomenon known as rectification
these channels are key in maintaining the resting membrane potential
kir inward rectification channels maintain vm
outward current of potassium is strongly inhibited when membrane potential is +ve
inward current is favoured when membrane potential is -ve
allow potassium ions to flow inward (into the cell) more readily than they allow outward flow
this works against the eletrochemical gradient
structure of inward rectifying potassium channels
4 subunits (tetrameric)
each subunit has two transmembrane helices
pore region formed by p-loop= selectivity filter
intracellular region has magnesium/ATP binding site
does not have a voltage sensing domain
structure of alpha-helix transmembrane domain
alpha helix consists of a regular repeating pattern of hydrogen bonds between the backbone atoms of the polypeptide chain
alpha helic is hydrophobic interacts with hydrophobic interior of PLB=anchor protein
S4 microdomain
N V R (R) V V Q I F R I M (R) I L (R) I F (K) L S (R)
(argenine and lysine) form voltage sensing microdomain
voltage sensing domain is…
conserved
across ALL voltage gated channels
but the precise
mechanism of voltage
sensing may not be the
same in all
P-LOOP and ion selectivity
P-LOOP forms the ion selectivity filter by projecting down into the pore of the channel to a constriction half way down and determines which ions can pass
classes of k+ channels
2TM- Kir (inward rectifier)
4TM- 2 pore domain
voltage gated
SK
Slo
Kv1.x and Kv2.x (voltage gated from Kv family)
delayed rectifiers that are responsible for repolarisation and fAHP (fast afterhyperpolarization)
this means potassium channels open later than sodium channels
SK and BK (BK from Slo1)
calcium activated potassium channels responsible for repolarisation and the mAHP (medium afterhyperpolarisation)
SK and BK determined by size of current (BK characterised by having a larger pore size and a greater conductance compared to SK channel)
sodium channels are not tetramers (4 subunits)…
na+ channels are composed of a single polypeptide chain – the alpha subunit
all four channel ‘subunits’ and incorporated into the alpha subunit
the alpha subunit is associated with one or more regulatory beta subunits
how many separate alpha subunits of the sodium channel are there?
9
sodium channel gating mechanism
activation gate opens very fast=very quick sodium influx
inactivation gate closes slowly (same time scale of potassium channel opening) preventing further sodium influx
this creates absoulte (sodium cannot be opened at all) and relative refractory period
calcium channel structure
similar family to sodium, same alpha subunits but have many more regulatory beta subunits
high voltage activation (HVA) calcium family
L-type (post-synaptic)
P/Q-type (pre)
N-type (pre)
R-type (pre)
throughout the brain
low voltage activation (LVA) calcium family
T-type (pre)
thalamus= particularly important in absence epilepsy
alpha helices and microdomains
transmembrane alpha helix proteins can be incorporated into lipid rafts/microdomains (specialized regions within the lipid bilayer)
what is the ion selectivity filter?
ion selectivity filter is a narrow region within the pore of the channel where ions pass through during channel opening
