Ion channels Flashcards
Where are ion channels found?
all cells
What is the structure of ion channels?
Heteromultimeric integral membrane proteins with selectivity filter loop and hydrophilic residues lining water filled pore
What membrane voltage changes are associated with action potentials?
-70mV resting potential maintained by K+ channels and Na+/K+ pump ligand gated Na influx channel threshold at -55mV opens vNa+ channels \+10mV opens vK+ for efflux Hyperpolarisation for unidirectional
How can ion currents be observed?
Patch clamping with suction seal to measure V/current changes of one channel
What functions do ion channels have?
Pain
Immune responses
cardiac rhythms
How can ion channels be targetted to treat disease?
Ca blockers in angina
CNS Ca blocked by ziconotide for pain
Na in anti-epileptics
diabetes
What are the 2 types of channelopathies?
Disturbed function of channel subunits or disturbed regulation
How can channelopathies be developed?
Congenital or aquired mutations
What are the congenital channelopathies?
Cystic fibrosis
Neonatal diabetes
Long QT syndrome
How is cystic fibrosis caused?
Mostly caused by ∆F508 producing only 10% functional fold of ABC-channel so no Cl/Na/osmosis efflux to thin mucus.
Results in breathing difficult, scarring and infection
Affects lungs, pancreas and sweat glands
How is neonatal diabetes caused?
SUR1 does not detect ATP to close K+ efflux channel. No depolarisation and no insulin secretion
How can neonatal diabetes be treated?
Glibenclamide ATP analogue blocks sulphonylurea receptor
How many HERG channel mutations prevent repolarisation of cardiac muscle?
30
What are the aquired channelopathies?
Tetrodotoxin
Dendrotoxin
HIV
Terfenadine
How does tetrodoxin act?
peptide blocks vNa channels so no depolarisation
respiratory failure
