Week 1 Lecture 4 Flashcards
What are the two types of post-synaptic receptors?
Ionotropic and metabotropic
What is an ionotropic receptor
Directly open channels
What is a metabotropic receptor?
Initiates a signalling cascade which activates enzymes
What is ionotropic effects?
Binding of transmitter to post-synaptic membrane opens ion channels which result in changes in the post-synaptic membrane potential called post-synaptic potential (PSP)
What are the two types of post-synaptic potentials?
EPSPs (excitatory) and IPSPs (inhibitory)
What do EPSPs correspond to?
the opening of ion channels specific for cations, Na+ and K+, depolarizing
What do IPSPs correspond to?
the opening of ion channels specific to Cl- or K+, hyperpolarizing
What are nicotinic receptors?
The ionotropic receptor for acetylcholine
What are the ligands for ionotropic receptors?
Acetylcholine, glutamate, GABA and glycine
What is GABA?
An inhibitory transmitter, generates IPSPs, drugs that enhance the effect of GABA (i.e. benzodiazepines) are often used to treat anxiety and insomnia, reduce the communication between synapses
Can the ligand that act on ionotropic receptors also act on metabotropic receptors?
Yes, all the ligands that act on ionotropic receptors can act on metabotropic receptors. The transmitter does not determine the effect, the receptor does
What is metabotropic effects?
Binding of a ligand to the post-synaptic metabotropic receptor activates an enzyme, that is usually G-protein coupled, that either produces or destroys 2nd messengers.
What are examples of second messengers?
cAMP, cGMP, InP3
What do second messengers do?
activate enzymes like phopshokinases, which phosphorylates proteins
Why is the phosphorylation of proteins significant?
The phosphorylation of proteins results in a conformational change that changes the function of the protein e.g. the phosphorylation of ion channels may open/close them
What is the difference between the ionotropic and metabotropic effect?
- The ionotropic effect is fast while the metabotropic effect takes time
- The ionotropic effect results in a change in membrane potential while with the metabotropic effect there does not have to be a change in membrane potential
What is the beta-andrenoreceptor?
The metabotropic receptor for Noradrenalin (NA)
What is the signalling cascade associated with the beta-adrenoreceptor? (4)
- Binding of NA activates adenyl cyclase via conformational change in G-coupled protein
- Adenyl cyclase produces cAMP
- cAMP activates kinases which phosphorylate Ca++ channel protein which increases Ca++ influx
What are beta-blockers?
Block interactions between NA and beta-adrenoreceptors which decreases calcium availability resulting in less activity
What are ligands for metabotropic receptors?
ACh = muscarinic receptor
Peptides = substance P, beta-endorphin
Catecholamines = noradrenaline and dopamine
Serotonin
Purines = adenosine, ATP
Gases: NO, CO
Where are PSPs generated?
They are generated in inexcitable membrane e.g. neuronal dendrites and cell bodies where there is not a high density of voltage-gated Na+ channels
What is the trigger zone?
The nearest excitable membrane at the beginning of the axon
How are PSPs generated?
The binding of transmitter
How do PSPs spread?
PSPs spread across the membrane through passive conduction to get to the trigger zone.
Why is a single EPSP not enough to bring the trigger zone to threshold?
Biological tissue is not conductive, potential is lost while it moves across the membrane. Therefore, many PSPs summating is required to reach threshold
What are the two types of PSP summation?
Spatial and temporal summation
What is spatial summation?
Large number of EPSPs have to be activated simulataneously
What is temporal summation?
EPSPs last 30-40 ms, thus successive inputs generates EPSPs that add pre-existing EPSPs, high frequency EPSPs required
Where are IPSPs usually located and why is the location significant?
At the cell soma, which is between where EPSPs are generated and the trigger zone. This is location gives IPSPs an advantage since they can shunt EPSP potentials
How do IPSPs shunt depolarizing EPSP potentials?
IPSPs involve the opening of Cl- channels which have a equilibrium potential of -70 mV (very close to RMP) which brings the membrane potential back to -70mV when the membrane is depolarized, essentially preventing excitation.
Which is more important IPSPs or EPSPs and why?
IPSPs, because there are precise and control/shape information
What is a spike train?
The sustained depolarization of the trigger zone associated with the continuous stream of action potentials.
What does a spike train tell the brain?
That there is a very strong and prolonged stimulus present
What is necessary for a spike train to be generated?
Hyperpolarization is required for a spike train to occur because following an AP voltage-gated Na+ channels are closed and can only be opened once the RMP is reached therefore hyperpolarization is required to re-open them quickly
