BMS303 Lecture 7 Ligand-Gated Ion Channel

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  • Created by: Mollie
  • Created on: 17-01-18 20:04
There are 4 functional roles which ligand gated ion channels are important for, what are they?
1) Important at fast chemical synapses & play role in excitatory and inhibitory 2) Nociception 3) Mechanosensation 4) Autocrine and paracrine signalling (e.g P2X receptor)
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What are the main features of glycine receptors?
It is an inhibitory receptor mediated by a chloride channel and its ligand is glycine. They are found in the spinal cord and brain stem and is responsible for fast inhibitory synaptic transmission
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In addition to glycine receptors' Cl channels, GABAa receptors are also CL- channel mediated. Why do both Cl- channels have an inhibitory effect in the CNS?
They cause membrane potential to shift in a more negative direction making it harder to fire an action potential
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What are the three basic classes of the excitatory proteins Ionotropic glutamate receptors?
AMPA, NMDA, Kainate
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What is the structure of Glycine receptors and how do they impact membrane potential?
They are made up of 3 alpha1 subunits and 2 beta subunits all of which are required for the channel to be functional. The channel has a one pore and one binding site and acts to hyperpolarize the membrane potential via its CL channel
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How does glutamate activation of its receptor resulting in an EPSP which makes it easier to fire an action potential?
EPSPs are excitatory post synaptic potentials are depolarisations making the Vm more negative than the Nernst potential for cations so the driving force is for inward cation movement (inward cation EPSC)
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Why does the activation of glycine receptors result in an Inhibitory Postsynaptic Synapse Currents?
The receptors induce an IPSP by inducing a hyperpolarizing shift which drives the Vm toward the Nernst for Cl ions. As the Vm is more positive than the Nernst for Cl so there is Cl influx & the outward current is the IPSC
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What is the proper name for startle syndrome?
Hyperkplexia, it can occur as both autosomal dominant and recessive forms
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Hyperekplexia (GlyR mutations) in infants is characterised by; hypertonia (increases the risk of SIDS), enhanced startle reflex, apnea. The symptoms are life threatening and induced by auditory and tactile stimuli. What is different in adults?
Hypertonia disappears, auditory and tactile stimuli still induce enhanced startle reflex. It is no longer life life threatening but adults experience falls and injuries
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Clonazepam which is a benzodiazepine that activates GABAr Receptors, why is this an effective treatment for Hyperekplexia?
Hyperekplexia is the result of enhanced motor response, while response physiology is normal there is a defect within the gain & modulation so they have reduced inhibition of the response from the CNS. GABArR is a CNS inhibitory receptor
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When over expressing GlyR alpha subunit mutant in xenopus oocytes and comparing the currents produced at different concs of Glycine what was observed?
10x as much glycine was needed to activate mutant channels and produce a current and the maximum current produced in mutants is much smaller. This makes it difficult to hyperpolarize the membrane so its harder to inhibit action potentials
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Would a normalised response curve showing the impact of mutations in GlyR's alpha subunit compared to beta find that they are equally responsible for the channel's sensitivity?
No, beta subunit does not change the sensitivity of the channel to glycine however when the alpha subunit is mutated the sensitivity is highly reduced as there is a large increase in EC50 giving a loss of function phenotype
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In addition to giving rise to smaller currents, how else does the P250T mutation in GlyR differ from WT proteins
They also show a greater desensitisation to glycine
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How are recessive heterozygous GlyR mutations characterized in their expression of GlyR receptors.
This mutation impacts channel trafficking while dominant mutations do traffick to the membrane. So heterozygous mutants have cell surface glycine receptor levels between that of WT and homozygous recessive mutants
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What were the two main observations from GlyR 271Q transgenic mice?
In spinal cord neurons IPSC of transgenic mice is a lot smaller than the WT. Secondly their GABA receptors are also negatively affected although this is not the case in humans
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Card 2

Front

What are the main features of glycine receptors?

Back

It is an inhibitory receptor mediated by a chloride channel and its ligand is glycine. They are found in the spinal cord and brain stem and is responsible for fast inhibitory synaptic transmission

Card 3

Front

In addition to glycine receptors' Cl channels, GABAa receptors are also CL- channel mediated. Why do both Cl- channels have an inhibitory effect in the CNS?

Back

Preview of the front of card 3

Card 4

Front

What are the three basic classes of the excitatory proteins Ionotropic glutamate receptors?

Back

Preview of the front of card 4

Card 5

Front

What is the structure of Glycine receptors and how do they impact membrane potential?

Back

Preview of the front of card 5
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