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07
Biophysics III
39
Pharmacology
Undergraduate 1
12/27/2016

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Term
What does the patch-clamp technique allow?
Definition
characterise ion channel properties and their contribution to neuronal firing patterns
Term
Describe a cell attached patch-clamp configuration
Definition
membrane patch is left intact
Term
Describe a whole cell patch-clamp configuration
Definition
membrane patch is disrupted by briefly applying strong suction. The interior of the pipette becomes continuous with the cytoplasm
Term
Describe an inside out patch-clamp configuration
Definition
patch pipette is attached to cell membrane and is then retracted to break off a patch of membrane
Term
Describe an outside out patch-clamp configuration
Definition
pipette is retracted during the whole-cell configuration, causing a rupture and rearrangement of the membrane
Term
At what threshold are M-type K+ channels activated?
Definition
-60mV
slow activation
Term
What does M channel activity define?
Definition
firing patterns
Term
Define depolarisation
Definition
A reduction of charge separation, leading to a less negative membrane potential
Term
Define hyperpolarisation
Definition
An increase in charge separation, leading to a more negative membrane potential
Term
What are graded potentials?
Definition
Changes in membrane potential that do not lead to the opening of gated ion channels
Passive responses of the membrane
Term
What type of current comes from a positive current flow out of the cell?
Definition
outward current
Term
What type of current comes from a negative current flows in to the cell?
Definition
inward current
Term
What type of current comes from a negative current flow out of the cell?
Definition
If negative current flows out of the cell e.g. Cl- flow out of the cell, then this is effectively a positive current.
Term
What type of current comes from a positive current flows in to the cell?
Definition
If positive current flows into the cell e.g. K+ flow into the cell, then this is effectively a negative current.
Term
Describe the driving force and therefore the flow direction for K+ at:
a) -10mV
b) -110mV
c) -100mV
Definition
c) at -10mV, there will be a positive driving force so K+ will flow outwards.
b) at -110mV, there will be a negative driving force so K+ will flow inwards.
c) -100mV, there will be no driving force so K+ will not flow.
Term
Describe the driving force and therefore the flow direction for Na+ at:
a) +80mV
b) 0mV
c) +70mV
Definition
a) +80mV, there will be a positive driving force so Na+ will flow outwards.
b) 0mV, there will be a negative driving force so Na+ will flow inwards.
c) +70mV, there will be no driving force so Na+ will not flow.
Term
Describe the driving force and therefore the flow direction for Cl- at:
a) +50mV
b) -100mV
c) -50mV
Definition
a) +50mV, there will be a positive driving force so Cl- will flow outwards.
b) -100mV, there will be a positive driving force so Cl- will flow inwards.
c) -50mV, there will be no net driving force so Cl- will not flow.
Term
Describe the driving force and therefore the flow direction for Cl- at:
a) >0mV
b) <0mV
c) 0mV
Definition
a) at voltages > 0mV, there will be a positive driving force so cations will flow outwards.
b) at voltages < 0mV, there will be a negative driving force so cations will flow inwards.
c) at 0mV, there will no net driving force on any cation.
Term
What are the 4 basic types of neuronal firing?
Definition
1. phasic neurone
2. tonic neurone
3. accommodating neurone
4. spontaneously active neurone
Term
Describe and draw a phasic neurone
Definition
a neurone that fires in ‘bursts’ or ‘pulses’.
Term
Describe and draw a tonic neurone
Definition
a neurone that is constantly – ‘tonically’ – active as long as an input is detected.
Term
Describe and draw an accommodating neurone
Definition
a neurone with multiple discharges but with decrementing (decreasing gradually) frequency.
Term
Describe and draw a spontaneously active neurone
Definition
a neurone that fires or ‘bursts’ at a constant frequency. Example: pacemaker potential.
Term
What are firing properties of neurones defined by?
Definition
their ion channel expression profile
Term
What is M-current?
Definition
a type of non-inactivating potassium current
Term
Describe the M-channel
Definition
- a voltage-gated K+ channel
- activity defines firing patterns
Term
When is an M-channel open?
Definition
at rest and even more likely to be open during depolarisation
Term
What happens when the muscarinic acetylcholine receptor (MAChR) is activated?
Definition
M channels are inhibited
Term
How does M-channels prevent an AP?
Definition
1. Initial depolarisation of a neurone increases the likelihood that M-channels will open.
2. M-channels generate an outward K+ current.
3. K+ efflux counteracts Na+ influx in action potential. Overall result: full action potential is prevented.
Term
How does ACH cause M-channel inhibition?
Definition
1. 1 molecule of ACh binds to mAChR.
2. Gq G-protein causes the hydrolysis of PIP2 to IP3.
and IP3 dissociates from the membrane into the cytoplasm. When M-current is restored, it moves back to the membrane.
3. IP3 causes intracellular increase in Ca2+
4. inhibitor
Term
What effect does mAChR have by inhibiting M-channels?
Definition
excites sympathetic neurones
Term
How do mAChR inhibit cardiac muscle cells?
Definition
by activating G-protein-coupled inwardly rectifying K+ (GIRK) channels. When opened, these K+ channels result in hyperpolarisation of the cell.
Term
In simple terms, what effect does ACh have when it binds to M1 receptors?
Definition
M1 -> Gq -> M current inhibition -> excitation
Term
In simple terms, what effect does ACh have when it binds to M2 receptors?
Definition
M2 -> Gi -> GIRK activation -> inhibition
Term
How can rhythmic activity be generated?
Definition
by a combination of currents with various voltage-depedent and ion selectivity
Term
In addition to your ‘minimal’ set of voltage-gated Na+ and K+ channels, what else would you need?
Definition
1. Voltage-gated Ca2+ channels to raise intracellular Ca2+ after the burst of action potentials.
2. Ca2+-activated K+ channels to provide long-lasting afterhyperpolarisation.
3. Hyperpolarisation-activated non-selective cation channels (“Ih”) to stop and invert repolarisation.
4. T-type Ca2+ channels to ‘pick-up’ Ih-mediated depolarisation.
Term
What do GABAA-mediated postsynaptic responses depend upon?
Definition
the [CL-]i
Term
How can opening of Cl- be inhibitory?
Definition
In ionotropic GABAA receptors, binding of GABA molecules to their binding sites in the extracellular part of the receptor triggers opening of a chloride ion-selective pore. The increased chloride conductance drives the membrane potential towards the reversal potential of the Cl¯ ion which is about –65 mV in neurons, inhibiting the firing of new action potentials.
Term
Can opening of Cl- be excitatory?
Definition
yes
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