PSL300H1 Lecture Notes - Lecture 4: Ion Channel, Ligand-Gated Ion Channel, Substance P
PSL300
Lecture 4: Neurophysiology 4
Post Synaptic Receptors
• Transmitter agent diffuses across synapse and binds to a specific site on a receptor protein embedded in
postsynaptic membrane
• Binding of transmitter causes a change in shape of the receptor protein
• Receptors are either
o Ionotropic (directly opens channels)
o Metabolic (initiates a metabolistic cascade to activate enzymes)
• Receptor determines the effect, not the transmitter
Ionotropic Effects
• Ligand binding opens an ion channel
• Binding of the transmitter to the post-synaptic membrane results in change in the post-synaptic membrane
potential, this is called the post synaptic potential (PSP)
• The duration of PSP is about 20-40 ms (as long as the transmitters are present in the synaptic cleft)
• Ion channel may be specific for cations (Na+, K+) → EPSP (depolarizing)
o Excitatory Post Synaptic Potential
• Ion channel may be specific for Cl- or K+ ion → IPSP (hyperpolarizing
o Inhibitory Post Synaptic Potential
• Nicotinic Receptor for Acetylcholine
o The channel is closed when nothing is bound to the receptor
o When Ach binds to the receptor the channel will open
▪ The open cation channel will allow cation to come in and depolarize the membrane
▪ Generate fast EPSP
o Also has the ability to bind nicotine
• The ligands for the ionotropic receptors (transmitters that can act on ionotropic receptors) are principally:
o Acetylcholine (Ach)
o Glutamate
o GABA
o Glycine
• All these ligands can act on the metabotropic receptors; it’s the receptor that determines the effect not the
transmitter
Metabotropic Effects
• Binding of the ligand to the post-synaptic metabotropic receptor activates an enzyme that is usually G-protein
coupled
• The enzyme facilitation will result in increased production or destruction of 2nd messengers
o The 2nd messengers are either cAMP, cGMP, or InP3
o 2nd messengers then activate other enzymes, e.g. phosphokinases which phosphorylate the membrane
proteins or other proteins in the cytoplasm
o If you phosphorylate membrane proteins (i.e. ion channels) → result in modulation of ion currents
• The metabotropic receptor activation takes time
• Moreover, it is not necessary that there is any change in the MP, it might be all internal metabolic effect
• But if you influence an ion channel through the metabolic effect (i.e. through phosphorylation), the change in MP
will develop slowly (slow EPSP, slow IPSP)
• Change is slow because of it has to go through all the enzyme activity first before influencing the ion channels
• Ligands for metabotropic receptors
o Ach: Muscarinic receptor
o Peptides: substance P, ß-endorphin, ADH
o Catecholamine’s: noradrenaline, dopamine
o Serotonin
o Purines: adenosine, ATP
o Gases: NO, CO
