voltage gated ion channels Flashcards
identify families of VGIC
and their general structure
Sodium channels (NaV): sodium influx
responsible for the depolarization (initiation) of the action potential in excitable cells, such as neurons, heart and muscle cells.
Calcium channels (CaV): calcium influx
responsible for calcium influx that promotes neurotransmitter release and muscle contractions in skeletal cardiac and smooth muscle.
Potassium channels (KV): potassium efflux
involved in repolarization of the action potential and control of resting membrane potential. limit AP and recover resting membrane potentials.
describe the general structure of voltage gated ion channels
pore formed from alpha subunits
calcium and sodium channels: 1 x 24 TM unit (4 domains 6TM segments)
potassium channels: 4 x 6 TM subunits
S4 segment contains positively charged amino acid residues that act as voltage sensors (s1-s4 voltage sensing region)
S5-S6 segments have selectivity filter selective for ions based on size and charge density (s5-s6 pore region)
extra beta subunits with one TM unit and large extracellular domain on both sides
what is the effect of local anaesthetics on NAv channels
ex: benzocaine
unionized form cross PM and get protonated (ionized) in the intracellular environment due to lower pH. protonated form binds to the inside of activated state VGSC to inactivate action potential initiation
ester anaesthetics metabolised by cholinesterases (short lasting)
amide anaesthetics metabolised by liver amidases (long lasting)
what is the effect of anti convulsants on NAv channels
VGSC inhibitors in CNS treat epilepsy
ex: phenytoin
unionized form cross PM and get protonated (ionized) in the intracellular environment due to lower pH. protonated form binds to the inside of activated state VGSC to inactivate action potential initiation
what is the effect of anti arrhythmics on NAV channels
VGSC inhibitors in CNS treat cardiac arryhtmias
ex: lidocaine
unionized form cross PM and get protonated (ionized) in the intracellular environment due to lower pH. protonated form binds to the inside of activated state VGSC to inactivate action potential initiation
what are the types of CAv channels
L (long lasting)
Cav 1.1-1.4
large conductance (more influx over longer period of time) . activated above -10mV.
N (neuronal)
Cav 2.2
intermediate conductance activated above -10mv.
PQR
Cav 2.1 and 2.3
similar to N type.
T (transient)
Cav 3.1-3.3
small conductance activated above -70mV (low threshold).
give examples of effects of inhibitors and activators on CaV channels
L type blockers :
prevent opening of voltage gated calcium channels
dihydropyridines like nifedipine acts on vascular smooth muscle
phenylalkylamines like verapamil acts on cardiac tissue (angina and arrhythmia)
benzothiazepines like diltiazem on both
to decrease contractions on these tissues
dihydropyridine analogues used to stimulate contractions in vitro
describe the different types of potassium channels
4x6TM
Kv 1.x-12.x
voltage sensitive. all blocked by TEA.
BK/IK/SKca
calcium and voltage sensitive channels. (calcium influx activates potassium efflux.
2TM
Kir 3.x
inwardly rectifying (passes positive charge inside easier)
activated by GPCR
inhibited by 4-aminopridine
kir 6.x
inwardly rectifying activated by SUR
describe the theraputic exploitation on types of Kv channels
complex of Kir 6.1-6.2 with SURs
adp binding to sur induce opening atp binding induce closing
activators binds to SUR subunit of Katp channels opening them and causing increased hyperpolarization and potassium entry.
ex: diazoxide SUR1 in pancreas used for hypoglycemia. (decreases insulin secretion
nicorandil SUR2 in cardiac for angina
bind to SUR subunit closing them. lower potassium entry reduce adp induced opening. decreased efflux of potassium leading to depolarization. induce insulin release
blockers used for type two diabetes ex: tolbutamide and glibenclamide (sulphonylureas)
what are natural products that are inhibitors and activators of VGNa channels
inhibitor: tetrodotoxin
paralysis
activators: aconitine
inhibit inactivation by shifting voltage dependence to open at resting potential
