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 dpolarisation 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?
simply 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
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 has a positively
charged face which acts as the voltage sensor
P-LOOP forms the ion selecitivty filter
inward rectifying channel
ore forming region for all k+ channels is similar to the
inward rectifying channels
k+ ions flow into the cell rather than out (electrochemical gradient)
responsible for maintenance
of membrane potential
kir inward rectification channels maintain vm
kir channels set the resting membrane potential
vm is close to equilibrium potential of k+ channels
kir channels are NOT sensitive to voltage changes because it doesn’t have the voltage sensing domain
alpha-helix: the transmembrane domain
secondary structure
functional groups on outside surface
stabilised by hydrogen along the backbone
allows creation of microdomains
alpha helices are always right handed (hydrogen by thumb)
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
projects 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
SL
Slo
Kv1.x and Kv2.x (voltage gated from Kv family)
delayed rectifiers that are responsible for repolarisation and the fAHP
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
SK and BK determined by size of current (BK=big)
sodium channels are not tetramers…
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)
low voltage activation (LVA) calcium family
