Ion Channels Flashcards
Define ion channels (5)
proteins
An aqueous pore connecting internal and external media
A gating mechanism that opens the pore
Selective permeability
preference of one type of ion over another
High transfer rate movement of many ions
leads to recordable
Ventricular Action potential (4)
1) rest - high K+, low NA+ and Ca2+ conductance
2)fast upstroke (membrane pot = -80 to 0) - inc. in Na+ (brief) , re. in K+, ca2+ inc slowly but lasts longer
3) stays at 0 for a 10 milliseconds
4) then repolarises (back to - figures)
What is electrophys?
recording of ion channels
+ve ions into cell = inward = downwards arrow
+ve ions out of cell = outwards = upwards arrow
What is a Voltage-dependent sodium channel channel?
big flow of na+ ions in
as soon as it reaches a plateau - it reduces immediately
Voltage-dependent sodium channels background- including the pharm + phys (4)
encode by 9 genes (SCNA1-9)
~2000 amino acids
Auxillary subunits increase amplitude: helps get the proteins to the channels
Biophysics:
-Rapid activation,
-Rapid N/C-terminal inactivation (not passing current but not closed)
Physiology:
-Nerve conduction
-Skeletal muscle (neuromuscular junction - NAChr)
-Cardiac AP
Pharmacology:
target for local anaesthetics,
Lidocaine
Lignocaine
Benzocaine
Tetracaine
Bupivacaine
Venom of spiders, wasps, snakes, scorpions, cone snails and sea anemone (3)
Veratridine
Batrachotoxin
Atracotoxin
Toxin free - see the rapid increase of na+ ions and then decreases by itself - inactivation
red = w/atracotoxin: = remove inactivation (current flow is dec. a bit but the decay of the channel current is much less) - also seen in ischaemic cardiomyocytes
poison found in pufferfish, blowfish, balloon fish,
toads, sunfish, porcupine fish, toadfish, globefish, and
swellfish
=a tetrodotoxin
TTX-s block a number of Na+ channels with a binding affinity of 5-15
TTX-r Na+ channels bind TTX with low μM affinity too.
TTX-r Na+ channels are located primarily in
cardiac tissue, TTX-s Na+ channels are in nerves and skeletal muscle
- pufferfish poisoning if too much - shut down skeletal muscles + nerves (otherwise should be a tingly mouth sensation)
How does a Voltage-dependent sodium channel open? (5)
the cavity in walls b/w a.a.’s 5-6 (pore-forming residue) - is where na+ ions pass through
made up of 4 repeating domains - each w/ 6 transmembrane domains
4th a.a. = voltage sensor: once detected it will cause a molecular kink to cause the ion channel to open + ions flow
selectivity filter - that allows just na+ flow through
What happens in resting cardiomyocytes when stim. by SAN (excitation)? (4)
1) resting config - pore is closed, no. of wells where ions linger, vestibule w/h20
2) as depol. starts - (partially activated): voltage sensors move out membrane = pulls ion channel open
3) open channel: ion flow (na+ hit the other newton’s cradle = fast transfer)
4) maintained depol. state = inactivation gate swings back in stopping/ occlusion= no ion flow
inactivated DOES NOT mean closed
What is a voltage gated potassium channel? (7)
similar : one domain of the 4 in na+ channels - made up of only 2 transmembrane domains
1/4 size of ca2+ and na+ channels
has two units that rise calcium or calmodulin levels = activation of channel
= not voltage gated ( get benefit from voltage) but requires rise in ca”+ to open
ion channel at front = form background ion current
middle units = affected by membrane stretch or pH changes
12 families - KCNA - KV1, 2,3 ,4 etc. = all have distinctive properties/shapes + all modified by auxiliary proteins
how does a voltage gated potassium channel work differently? (3)
protien goes in + out of membrane 6x
4th - a lot of +ve A.A.’s + pore is made up of S5-6 domains
incomplete - because it needs 4 voltage gated k+ channels of same fam - come together to form functional channel - tetramise (form tetramer) - can have homo/heter tetramer
how does a voltage gated potassium channel activate? (2)
1) resting
2) depol = s4 domain moves out of membrane =pore to be pulled apart= ion flow
Is the voltage gated potassium channel as brief as the sodium channel? (4)
k+ ion channels have diff. characteristics:
one opens slowly - stays open - little inactiv
one opens rapidly - closes/inactive pretty quick like na+ a lot of inact
(don’t live by themselves - are usually w/ reg. proteins)
Heart- gene product KCNE1 (auxiliary proteins) (4)
KV7.1
activates quickly + stays open
but in teh heart - lives in association w/ small protein - singles transmem domain encoded by gene KCNE1
= takes a lot longer to activate but is far bigger because aux unit (kcne1) helps ion channel get to mem, assemble + respond to voltage
hered diseases in heart - underlined due to damage to KCNE1 AND damage to KV7.1
2 types of k+ channel inactivation (2)
1) N: amino terminus (ball) get sucked into membrane
2) C: terminal inactivation is when outer mmebrane just collapses
Selectivity (4)
- Most K channels only permeable to K+, Rb+, NH4+.
- NOT Na+ or Ca2+
- Free Ca2+ outnumbered by Na+ and Cl- in the extracellular solution yet VDCCs conduct just Ca2+
- Some channels not discriminator
Selectivity-potassium (K) channels (4)
- K+ to pass at such high rates due to the combination of high selectivity and rapid throughput
- Protein seems to present no barrier at all, while simultaneously acting as a concrete wall to the smaller Na+ ion
- Biophysical experiments suggest a K channel contains a narrow ‘selectivity filter’ through which dehydrated K+ (but not Na+) fits precisely
Selectivity-summed up
on energetically stable due to interaction with channel dipoles (in h20)
Channel conformation can only embrace a
certain shaped ion (Woodstock the bird in
this case)
Summary (5)
ion channels are proteins that create selective pores opened by precise mechanisms
Think of the cardiac action potential
What features of the sodium channel are crucial for AP generation
What are the molecular mechanisms at work?
What features of the Kv channels are pertinent
for the cardiac AP?
K channel types?
