Questions on the synapse: transmission, and why it runs one way

Question 1

Describe what happens at a cholinergic synapse from the moment an action potential arrives at the presynaptic knob to the moment the cleft is cleared again.

Accepted Answer

B1 the arriving action potential depolarises the membrane of the knob, so voltage-gated calcium channels open and calcium ions diffuse in B1 the influx of calcium causes vesicles of acetylcholine to move to the presynaptic membrane and fuse with it, releasing their contents by exocytosis B1 acetylcholine diffuses across the 20 nm cleft down its concentration gradient and binds to receptor sites on the postsynaptic membrane B1 the receptors are sodium channels, so binding opens them, sodium ions diffuse into the postsynaptic neurone and depolarise it, and a new action potential begins if threshold is reached A1 acetylcholinesterase in the cleft hydrolyses the acetylcholine, and the products are reabsorbed into the knob and recombined using ATP from its mitochondria

Question 2

Explain how an inhibitory synapse reduces the chance that the postsynaptic neurone produces an action potential, and explain why inhibition is useful rather than a fault in the system.

Accepted Answer

B1 the receptors at an inhibitory synapse open chloride channels, letting negative chloride ions in, or potassium channels, letting positive potassium ions out B1 either movement makes the inside of the postsynaptic membrane more negative, so it is hyperpolarised rather than depolarised B1 a larger excitatory input is now needed to bring the membrane to the threshold of about −55 mV A1 this lets a postsynaptic neurone weigh positive against negative inputs, so signals are sharpened, unwanted movements are suppressed and the whole network does not fire at once

Question 3

A toxin from a marine snail prevents the voltage-gated calcium channels in presynaptic knobs from opening. Suggest the effect of this toxin on transmission at a neuromuscular junction, and suggest why an injection of extra acetylcholine into the cleft would not restore normal control of the muscle.

Accepted Answer

B1 calcium ions could not diffuse into the synaptic knob when an action potential arrived B1 without the calcium influx the vesicles would not move to the presynaptic membrane and fuse with it, so no acetylcholine would be released into the cleft B1 no receptors on the postsynaptic membrane would be occupied, so no sodium channels would open, the muscle fibre membrane would not depolarise and the muscle would be paralysed A1 injected acetylcholine would bind and depolarise the fibre, but the amount present would no longer depend on the impulses arriving, so the contraction could not be graded or timed by the nervous system

Question 4

An imbalance of serotonin in the brain is one of the factors that contributes to depression. Explain how a selective serotonin reuptake inhibitor (SSRI) can reduce the symptoms of depression.

Accepted Answer

B1 serotonin is released from the presynaptic neurone into the synaptic cleft and binds to receptors on the postsynaptic membrane B1 it is normally removed from the cleft by a transport protein that takes it back into the presynaptic neurone B1 an SSRI binds to this transport protein and blocks reuptake, so serotonin stays in the cleft for longer B1 serotonin goes on binding to the postsynaptic receptors, so transmission at serotonin synapses increases, which makes up for the reduced serotonin transmission linked to depression

Question 5

Explain why people with Parkinson's disease have difficulty controlling movement, and explain why they are treated with L-Dopa rather than with dopamine.

Accepted Answer

B1 dopamine-secreting neurones in the brain that are involved in controlling movement die B1 less dopamine is released, so fewer receptors on the postsynaptic neurones are stimulated, giving tremor, stiffness and slow movement B1 dopamine cannot cross the blood-brain barrier, so dopamine given as a drug would not reach the brain B1 L-Dopa can cross it and is converted to dopamine in the brain, so the surviving neurones release more dopamine

Question 6

Explain what determines the size of the excitatory postsynaptic potential produced by a single impulse, and explain why one impulse at one synapse does not usually trigger an action potential in the postsynaptic neurone.

Accepted Answer

B1 the size depends on how much acetylcholine is released, set by how many vesicles fuse, each holding a fixed quantity, and on how many receptor channels it opens; typically a few millivolts B1 reaching threshold from the resting potential of −70 mV requires a depolarisation of about 15 mV B1 a single small excitatory postsynaptic potential is far short of that on its own, so no action potential is triggered by one impulse at one synapse acting alone B1 threshold is reached only once several such potentials are combined, by spatial or temporal summation

Question 7

Explain how nicotine and curare can both bind to the acetylcholine receptor on a postsynaptic membrane, yet produce opposite effects on transmission.

Accepted Answer

B1 both nicotine and curare have a shape complementary to the acetylcholine receptor, so both are able to bind to it B1 nicotine binds and activates the receptor, opening its channel as acetylcholine would, so the postsynaptic membrane is depolarised and more impulses are produced B1 curare binds the same receptor but does not activate it, so the channel stays closed B1 while curare occupies the receptor, acetylcholine cannot bind there either, so no depolarisation occurs and transmission is blocked

Question 8

Compare an excitatory synapse with an inhibitory synapse, referring to the ions the postsynaptic channels let through and the effect each has on the chance of an action potential.

Accepted Answer

B1 at an excitatory synapse the postsynaptic channels let sodium ions in, whereas at an inhibitory synapse they let chloride ions in or potassium ions out B1 the excitatory synapse depolarises the postsynaptic membrane, making an action potential more likely, whereas the inhibitory synapse hyperpolarises it, making one less likely B1 both act by changing which ions cross the postsynaptic membrane, one moving it towards the threshold of about −55 mV and the other away from it B1 a postsynaptic neurone usually receives both kinds of input at once and sums them, so whether it fires depends on the balance between the two

Question 9

Transmission across a single synapse takes about 0.5 ms. A pathway containing four synapses also involves 6 ms of conduction along its neurones. Calculate the total time from stimulus to response, and calculate the percentage of that time accounted for by the synapses.

Accepted Answer

M1 total synaptic delay = 4 × 0.5 = 2.0 ms A1 total time from stimulus to response = 2.0 + 6 = 8.0 ms M1 percentage = synaptic delay ÷ total time × 100 = 2 ÷ 8 × 100 A1 25%, one quarter of the total

Question 10

Explain why transmission across a synapse can happen in one direction only, and explain why this matters for a reflex arc.

Accepted Answer

B1 vesicles of acetylcholine are found only in the presynaptic knob, so the neurotransmitter can only be released on that side B1 receptors complementary to acetylcholine are found only on the postsynaptic membrane, so it can only be detected on the other side A1 an impulse arriving at the postsynaptic side would find nothing to release and nothing on the far side to detect it, so a reflex arc runs reliably from receptor to effector and never backwards

Question 11

Compare spatial summation with temporal summation at a postsynaptic neurone.

Accepted Answer

B1 spatial summation adds inputs arriving at the same time from several different presynaptic neurones, whereas temporal summation adds impulses arriving in quick succession from a single presynaptic neurone B1 in spatial summation the depolarisations are produced at different points on the membrane at once, whereas in temporal summation the transmitter from the first impulse has not yet been hydrolysed when the second arrives B1 both reach threshold by adding small excitatory postsynaptic potentials together, and in neither case could threshold be reached by one impulse at one synapse acting alone

Question 12

MDMA, the active substance in Ecstasy, binds to the serotonin reuptake proteins in presynaptic membranes. Explain how MDMA raises mood, and suggest why users often report low mood in the days that follow.

Accepted Answer

B1 MDMA blocks the reuptake of serotonin and also causes serotonin to be released from the presynaptic neurone into the cleft B1 the concentration of serotonin in the cleft rises, so more binds to postsynaptic receptors and the postsynaptic neurones are strongly stimulated B1 afterwards the presynaptic neurones' stores of serotonin are depleted, so less is released and serotonin transmission falls

Question 13

Nicotine and cobra venom both bind to acetylcholine receptors. Compare their effects on transmission at a neuromuscular junction.

Accepted Answer

B1 both have shapes complementary to the binding site of the acetylcholine receptor on the postsynaptic membrane B1 nicotine mimics acetylcholine: it opens the receptor channels, sodium ions enter and the membrane is depolarised as though acetylcholine had bound B1 cobra venom binds without opening the channels and stops acetylcholine binding, so the muscle fibre is not depolarised and the muscle is paralysed

Question 14

Name the presynaptic structure that contains vesicles of acetylcholine and voltage-gated calcium channels, name the ion that enters it when an action potential arrives, and name the process by which the vesicles release their contents into the cleft.

Accepted Answer

B1 the synaptic knob B1 calcium ions, entering down their gradient B1 exocytosis, the vesicles fusing with the presynaptic membrane

Question 15

Cocaine blocks the protein that normally removes dopamine from a synaptic cleft by reuptake. Suggest what this does to the concentration of dopamine in the cleft after an impulse, and suggest what effect this has on how often the postsynaptic neurone fires.

Accepted Answer

B1 without reuptake, dopamine is not removed from the cleft as quickly as normal, so its concentration there stays higher for longer after each impulse B1 the transmitter remains bound to postsynaptic receptors for longer, or is able to re-bind after dissociating, so a single impulse produces a longer-lasting depolarising effect B1 the postsynaptic neurone therefore fires more often, or is brought to threshold more easily, than it would be with reuptake working normally

Question 16

Organophosphate insecticides inhibit acetylcholinesterase. Explain why they cause an initial burst of increased firing at a synapse before transmission fails altogether.

Accepted Answer

B1 acetylcholine is not hydrolysed, so it builds up in the cleft and stays bound to the postsynaptic receptors B1 the receptor channels stay open and sodium ions keep entering, so the postsynaptic neurone fires repeatedly at first B1 a membrane held continuously depolarised cannot reset its voltage-gated sodium channels, which are needed to generate a new action potential, so transmission eventually fails, a state called depolarisation block

Question 17

Describe the structure of a cholinergic synapse, naming a component on the presynaptic side, one in the cleft, and one on the postsynaptic side.

Accepted Answer

B1 on the presynaptic side, the synaptic knob contains vesicles of acetylcholine and voltage-gated calcium channels B1 the cleft, about 20 nm wide, contains the enzyme acetylcholinesterase, which hydrolyses the transmitter; acetylcholine diffusing across the cleft also scores B1 on the postsynaptic side, receptor proteins with binding sites complementary to acetylcholine act as sodium channels

Question 18

Give the name of the neurotransmitter used at a cholinergic synapse, and give the name of the enzyme that removes it from the synaptic cleft.

Accepted Answer

B1 the neurotransmitter is acetylcholine B1 the enzyme is acetylcholinesterase, which hydrolyses it into choline and ethanoic acid

Question 19

State the approximate width of the synaptic cleft, and state how acetylcholine crosses it.

Accepted Answer

B1 about 20 nm B1 by diffusion down its concentration gradient, requiring no energy