Excitatory and inhibitory neurotransmission (look at these along with Introduction to Neurones, Nerve Conduction and Synaptic Transmission)

Question 1

Define what each of the following is:

1. EPSP (excitatory postsynaptic potential)
2. IPSP (Inhibitory PSP)
3. Graded potential

Answer 1

1. EPSP (excitatory postsynaptic potential) - A depolarizing change in rmp caused by the actions of excitatory neurotransmission. Multiple EPSPs or very large EPSPs can cause rmp to cross threshold and result in an Action Potential (AP)
2. IPSP (Inhibitory PSP) - negative change in rmp caused by release of an inhibitory neurotransmitter. Inhibits crossing of the threshold and inhibits AP.
3. Graded potential - a change in the rmp caused by an EPSP or IPSP, such a change is caused by (inhibitory or excitatory) neurotransmitter release and is not of a magnitude large enough to cross threshold and result in an AP

Question 2

What is the typical ion concentration inside and outside a cell ? (intra and extracellular)

Answer 2

Question 3

How do drugs acting on Na+ and K+ (agonsits and antagonists)

Answer 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

Any drug that is an agonist of a K channel -> opens K channel, cause K flow out of cell, makes cell more negative and is therefore inhibitory

A K channel antagonist -> closes K channel, retains K in the cell, favours positive rmp and is therefore excitatory

Question 4

Go over this

Question 5

What are the 2 main modes of action of neurotransmitters in the post-synpatic cleft on ion channels ?

Answer 5

Essentially neurotransmitters may act directly or indirectly on ion channels

• Direct gating is by IONOTROPIC RECEPTORS. The receptor is an integral component of the molecule that forms the channel it controls
• Indirect gating is mediated by activation of METABOTROPIC RECEPTORS. Receptor and the channel it controls are distinct.

Question 6

WHat are the 2 major families of ligand-gated channels ?

Answer 6

1. GABA_A, Glycine and nicotinic ACh-gated channels - these are all pentamers
2. Gultamate receptor channels which are all tetramers

Question 7

What is the major excitatory neurotransmitter and what is its 2 main types of receptors and what is the main difference between the 2 of them

Answer 7

Gultamate - acts on ionotropic receptors; non-NMDA and NMDA. To allow Na and Ca in and K out of the cell, net result is an EPSP, depolarization, and excitation.

1. Non-NMDA ionotropic receptors - mediate fast excitatory synaptic transmission in the CNS
2. NMDA ionotropic receptors - contribute a slow component to the excitatory synaptic potential

Question 8

What is the main inhibitory neurotransmitter in the CNS and what receptors does it act on ?

Answer 8

GABA is the main inhibitory neurotransmitter in the CNS to allow Cl into the cell, net result is an IPSP, hyperpolarization, and inhibition

It acts on 2 types of receptors:

1. Ionotropic GABA_A receptor that operates a Cl- channel
2. GABA_B is a metabotropic receptor, often activates a potassium channel

Question 9

What is the other important inhibitory neurotransmitter to know about (not talking about GABA) and what receptors does it act on ?

Answer 9

Glycine - acts on a glycine ionotropic receptor that gates a Cl- channel ==> influx of Cl- ==> inhibition

Question 10

Describe the main differences in the action of inonotropic and metabotopic receptors

Answer 10

Ionotropic receptor gating of ion channels is rapid (milisecs), metabotropic slower (tens of ms – secs)

Iontropic channels function as on-off switches

Metabotropic receptors can close as well as open ion channels

Normally the slow actions of metabotropic receptors are insufficient to trigger an action potential. Rather they have MODULATORY SYNAPTIC ACTIONS:

• acting on channels in the presynaptic terminal to modulate transmitter release
• modulating transmitter-gated channels to regulate the size of the post synaptic potential
• modulate the resting and voltage-gated ion channels in the neuronal soma to alter e.g. resting Em and AP firing pattern

Question 11

What 2 types of transmission does cholinergic (ACh) transmission display (hint its essentially what was just talked about)

Answer 11

• Fast EPSP is due to activation of nicotinic (ionotropic) ACh receptors. Channels conduct Na+ and K+
• Slow EPSP follows activation of muscarinic (G protein- coupled) ACh receptors. ACh closes a K+ channel (M-type)

Question 12

Define each of the following terms:

1. Interneuron
2. Projection neuron
3. Excitatory neuron
4. Inhibitory neuron

Answer 12

1. Interneuron - a locally-acting neurone, typically releases GABA and so brings about an IPSP and inhibition, function is local processing of information
2. Projection neuron - a neuron responsible for conveying signals to other parts of the brain, typically releases Glutamate and so brings about an EPSP
3. Excitatory neuron - releases a depolarizing neurotransmitter (e.g. glutamate)
4. Inhibitory neuron - releases a hyperpolarizing neurotransmitter (e.g. GABA)

Question 13

At the synpatic cleft what are neurotransmitters released in and define this ?

Answer 13

• Discrete packages called quanta; varying quanta may be released
• A quanta refers to the release of neurotransmitter from a single vesicle
• The number of quanta released varies with the stimulus, think strong stimulus then more quanta release and vice versa