Week 2 - C - Pharmacology 3 - Excitatory and inhibitory neurotransmission

Question 1

In a neurone, the depolarization of a neuron leads to the opening of certain channels (eg Na,K,Ca) causing the release of a neurotrasmitter at the synapse of the neuron to the postsynpatic cell

• What are the normal directions of flow of these ions Sodium, potassium, calcium, chloride?
• And are they excitatory or inhibitory?

Answer 1

• Sodium depolarizes the cell as it flows in wards - this is excitatory
• Calcium depolarizes the cell as it flows in wards - this is excitatory
• Chloride flows into the cell however is negative and therefore hyperpolarizes the cell - this is inhibtory
• Potassium leaves the cell and therefore hyperpolarizes the cell -this is inhibitory

Question 2

Sodium depolarizes the cell as it flows in wards - this is excitatory Calcium depolarizes the cell as it flows in wards - this is excitatory Chloride flows into the cell however is negative and therefore hyperpolarizes the cell - this is inhibtory Potassium leaves the cell and therefore hyperpolarizes the cell -this is inhibitory Which ion conc. are higher outside or inside the cell?

Answer 2

Sodium, calcium and chloride ion concentration is higher outside the cell hence the influx of these ions when channels open Potassium ion concentration is greater inside the cell hence the efflux of these ions when the channel opens

Question 3

Any drug that is an agonist of a Na channel -> opens channel, causes Na flow in cell, causes excitation A Na channel antagonist -> closes channel, stops Na ion flow, favours inhibition…..e.g. local anaesthetics like lidocaine What effect does a potassium channel agonist and antagonist have on the cell?

Answer 3

A potassium channel agonist opens potassium channels causing potassium to leave the cell, this makes the cell more negative (hyperpolarizes it) and is therefore INHIBITORY A potassium channel antagonist closes the potassium channels keeping potassium in the cell and therefore making the cell more positive (depolariing the cell) and is therefore EXCITATORY

Question 4

What are the morphological regions of the neuron?

Answer 4

• Dendrites
• Soma
• Axon hillock and initial segment
• Axon
• Synapse

Question 5

Dendrites receive incoming signals; axons carry outgoing information What is the major output neuron of the cerebellum? What are the three layers of the cerebellum?

Answer 5

• Molecule
• Purkinje
• Granular layers

Purkinje cell layer is the main output layer of the cerebellum

Question 6

An action potential depolarizes the axon terminal. The depolarization opens voltage- gated Ca2+ channels and Ca2+ enters the cell. How does the opening of the voltage activated calcium channels cause a response in the postsynapcticcell?

Answer 6

The calcium entry triggers exocytosis of synaptic vesicles releasing neurotransmitters into the synaptic cleft The neurotransmitter binds to postsynaptic terminals causing a response

Question 7

Post-synaptic action of a Neurotransmitter 2 Modes of action. Neurotransmitters may act directly or indirectly on ion channels Direct gating is by what type of receptors? Indirect gating is by what type of receptors?

Answer 7

Direct gating is by Ionotropic receptors Indirect gating is by metabotropic receptors

Question 8

What is the difference in the way the ionotropic and metabotropic receptros work?

Answer 8

Ionotropic receptors means when the neurotransmitter binds to the postsynaptic terminal - the channels will open and allow flow of an ion Metabotropic receptors mean when the neurotransmitter binds to the terminal - a cascade is activated to allow the flow of the ion in the channel

Question 9

In ionotropic recpetors, when a neurotransmitter binds to the receptor, the ion channel is attached to the receptor and the channel opens How does this differ from metabotropic receptor ? Which type of receptor is faster between the two?

Answer 9

When a neurotransmitter attaches to the metabotropic receptor at the post synaptic terminal, this cause intracellular cascades to set off resulting in the eventual opening/closing of an ion channel at a separate site Ionotropic channels are far faster than metabotropic

Question 10

GABA, Glycine and nicotinic ACh-gated channels are pentamers What type of protein are glutamate gated channels?

Answer 10

Glutamate gated channels are tetramers

Question 11

What is the major excitatory neurotransmitter?

Answer 11

This would be glutamate

Question 12

Glutamate may also have inhibotry effects due to its response at which receptors?

Answer 12

May have inhibtory effects due to its action on Metabotropic channels

Question 13

Metabotropic Glutamate receptors don’t have an integral ion channel but exert their effect by activation of a second messenger cascade Role is modulation of neurotransmission. e.g. Presynaptic inhibition (inhibition of Ca2+ channels) What pathways are the ionotropic and metabotropic glutamate pathways important in distinguishing between?

Answer 13

They are important in discriminating between ON and OFF retinal pathways

Question 14

What is the major inhibitory neurotransmitter? Name another inhibitory neurotransmitter

Answer 14

GABA - y-aminobutryic acid is the major inhibitory Glycine is another inhibitory neurotransmitter

Question 15

Which inhibitory neurotransmitter is very important in the spinal cord? It is released by interneurones in spinal cord to inhibit antagonist muscles motoneurones

Answer 15

Glycine is this important neurotransmitter

Question 16

What is an interneuron?

Answer 16

They are usually found between efferent and afferent fibres in the spinal cord

Question 17

What do interneurons release in the spinal cord to inhibit antagonist muscle motoneurones? (ie they release a neurotransmitter to stop the flexors of the bicep working when you want the triceps to extend)

Answer 17

The neurotransmitter glycine is released as this is one of the inhibitory neurotrasmitters

Question 18

What effect does EPSP have on the resting membrane potenital? What is an EPSP? What can multiple EPSP cause?

Answer 18

Excitatory post-synaptic potential depolarize the resting membrane potential (rmp) Multiple e.p.s.p can cause the potenital to cross the threshold and cause an action potenital

Question 19

IPSP (Inhibitory PSP): negative change in rmp caused by release of an inhibitory neurotransmitter. Inhibits crossing of the threshold and inhibits AP. What is a potential that does not cross the threshold known as?

Answer 19

This is a graded potential

Question 20

When the incoming signals reach the postynaptic terminals of the dendrite, the neurotrasmitter will activate an ion channel If this is an excitatory neurotransmitter an excitatory ion channel will be activated causing the cell to depolarize The depolarizing of the cell if high enough will cross the threshold and release an action potential At what part of the neuron is this action potential released?

Answer 20

The action potential is released at the axon hillock

Question 21

What are the functional regions of the neuron again?

Answer 21

Input - dendrite, integrative - cell body, conductile - axon, output - synapse

Question 22

the major excitatory neurotransmitter, acts on ionotropic receptors to allow Na and Ca in and K out of the cell, net result is an EPSP, depolarization, and excitation. What is this? What ion channels does the major inhibitory neurotransmitter mainly act on?

Answer 22

This is glutamate The major inhibitory neurotransmitter - GABA (y-aminobutryic acid) acts mainly on chlorine channels causing influx of negatively charge chloride ions resulting in i.p.s.p , hyperpolarization and inhibition

Question 23

Summation of postsynaptic membrane potentials allows multiple synaptic inputs to be integrated What is the difference between spatial (multiple neurones) and temporal (single neuron) summation?

Answer 23

Spatial summation is where e.p.s.p and i.p.s.p are spatially distributed but occur at the same time Temporal summation is where e.p.s.p occur in temporal sequence such that a threshold is triggered The neuron cell body acts as a computer by integrating (adding or summing up) the incoming potentials.