Ion Channels - L3 | Flashcards

Question	Answer
What must be accounted for in terms of the size of the pore?	Ions are hydrated - surrounded by shell of water. Total size of ion includes shell of water and must be accounted for by the size of the pore.
What is an ion channel similar to? Why?	Ion channels are similar to enzymes in that they reduce the energy required for the ion to cross the pore - facilitates passage of hydrophilic ion just as enzymes facilitate a reaction.
How is ion flow facilitated?	Facilitated by pore substituting for water, ion is dehydrated as it travels through pore and then rehydrated upon exit.
What is the Kv1.2 channel?	Shaker channel
How was the Kv1.2 channel first discovered?	Mutated shaker channel in Drosophila, fly shakes in presence of anaesthetic gas.
What channel was discovered by MacKinnon?	KcsA channel extracted from streptomyces lividans.
As a result of the many (K+) channels with similar amino acid sequences in a variety of organisms, what was it possible to determine?	How properties of these K+ channels related to their structure.
What are the different techniques for studying ion channels? (8)	1) Electrophysiology - inward/outwardly rectifying, leak etc 2) Pharmacology ligands - toxins 3) Physiology ligands - agonists etc 4) Cloning, sequencing and expression - eg. Ach receptor from Torpedo ray 5) Mutagenesis - see effect of mutation 6) Antibody binding - localisation and effect 7) X-ray crystallography/EM/Spectroscopy 8) Computer modelling
What determines the charge of the pore and therefore which ion can pass through?	The amino acid residue
Describe the carbonyl residue	R I C=O I R
How does the residue function in the pore? What does this mean in terms of ion selectivity?	1) The residue inside the pore replaces the water residue - favourable reaction which allows the pore to move through. 2) The selectivity of ion is based on its size without the water shell
How many K+ interact with the Kv selectivity filter? What causes the expulsion of a K+ across the ion channel?	1) 2 2) Entry of a third K+ ion causes electrostatic repulsion
What prevents 'too tight' binding and ensures flow of ions?	Ion repulsion
What determines the direction of ion flow?	1) Voltage conditions 2) Ion concentrations 3) Gating of ion channel
When can a rectifying channel be made to open in the other direction? What does this show?	Under laboratory conditions - pore model isn't directional.
How does the size of Na+ channels compare to K+ channels? Why don't they pass through Na+ channels?	Na+ ions are smaller than K+ ions. Despite being smaller they can't pass through K+ channels - ions must be the 'right' size to interact with the selectivity filter.
Give an example of a note very selective ligand gated channel - which ions does it allow to pass through?	NMDA - Ca2+, K+ and Na+
What is required to push an NMDA receptor into the open configuration?	1) Glycine and glutamate 2) Mg2+ block must be removed
What causes the gating currents? (4 steps)	1) H2O released 2) Helices in membrane move 3) Amino acid residues affected 4) Changes in membrane potential
How can antibodies be used to determine the structure of voltage gated channels?	Antibody fragment (Fab) binds to voltage sensitive portion of channel, pulling the 'arms' of the channel open.
What does each subunit of a voltage-gated channel consist of?	Six helical segments
Give 3 examples of tetrameric ion channels?	VG Na+, Ca2+ and K+ channels
Give an example of pentamer channel?	Nicotinic ACh receptor channel
Give an example of a hexamer?	Hemijunction or connexon
Which Kv subunits form the voltage sensitive domain? The pore domain? Are domains hydrophobic or hydrophilic?	1) S1 - S4 2) S5 - S6 Hydrophobic
What subunits make up a Kv channel?	Usually 4a and sometimes B subunits.
What is the function of B subunits?	Modulate pore - change gating/voltage and type of function
How do Kv(Ca) channel differ?	Have a internal Ca2+ binding domain
How do B subunits differ from a subunits?	Only two helical domains in a B subunit
What is the function of the S4 region, how does it vary between animals?	Voltage sensitive region Amino acid sequence maintained in most different animals
Where is the voltage sensitive region of the VG Na+ channel? Pore binding?	Outside of the cross section. Cross in middle of cross section.
Where does inactivation of the Na+ channels occur?	H between S6 and S1 of 3rd and 4th subunit
How do mutations which cause slow inactivation identify parts of channels?	Show which part of the pore is responsible for inactivation.
What is the KCNQ1 channel?	Outward delayed rectifier channel
What is the KCNK channel? What is it important for?	Leak channel - sets membrane potential
How many subunits does a KCNK channel consist of?	4 (m1-m4)
How else does a KCNK channel differ from the standard Kv channel?	Has two pores
What are the three other important properties of KCNK channels?	1) Open at rest but regulated ie by neurotransmitters 2) Selective 3) Can sense voltage (mechanism unclear)
How many domains does a Na a subunit have?	4
What mutation can occur at S5 of the a subunit? What does this result in?	Thr---Met Hyperkalemic periodic paralysis
What mutation can occur at the inactivating loop of the a subunit? (2) What does this result in?	1) Gly-Val or Thr-Met Paramyotonia congenita
What else causes hyperkalemic periodic paralysis?	Met---Val change at S6 of domain 4
What else causes Paramyotonia congenita? (2)	1) Leu - Arg at S3 of domain IV 2) Arg - His/Cys at S4 of domain IV
What does HYPP cause in horses?	Dog sitting
Which of the two Na+ channelopathies is temperature dependent?	PMC
What is a K+ channelopathy that can prove fatal? When is this seen in normal physiological conditions?	1) Long QT syndrome - K+ channel mutation results in long QT period, increases AP length in heart and can prove fatal. 2) Diving reflex - heart temporarily stops when diving into cold water as a result of long QT period.

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	Created by Anna Hogarth over 8 years ago