T1 L7: Physiology of the synapse Flashcards
What are some properties of ionotropic receptors?
They are ligand gated ion channels responsible for fast transmission. The ligands are neurotransmitters that cause a change in conformation which opens the central pore through which ions can travel.
Describe the structure of an ionotropic receptor
Channels made of 4/5 subunits that fold together to form a central pore
What is an agonist?
Works very similar to the natural neurotransmitter. It causes a physiological reaction
What is an antagonist?
A drug that blocks activity
Which ion do Glutamate receptors work with?
Na+
Describe how Glutamate ionotropic receptors work
An influx of ions causes an Excitatory Post Synaptic Potential (EPSP) that depolarises the postsynaptic neuron which causes an action potential
Describe how GABA ionotropic receptors work
An influx of ions causes an Inhibitory Post Synaptic Potential (IPSP) which hyperpolarises the postsynaptic neurone preventing an action potential
Which ion do GABA receptors work with?
Cl-
Which are the 3 types of ionotropic receptor that respond to glutamate?
NMDA, AMPA, and Kainate
What are the properties of non-NMDA receptors (AMPA and Kainate)?
They are fast opening channels permeable to Na+ and K+ responsible for early phase EPSP (excitation)
What are the properties of NMDA receptors?
They are slow acting channels permeable to Ca2+, Na+, and K+. They require extracellular glycine as a cofactor to open the channel. They are gated by Mg2+ which plugs the pore at resting potential. They are responsible for late phase EPSP and can only be activated when Glutamate is present
Describe when activity-dependent synaptic modification is used
In NMDA receptors. Mg2+ blocks the pore during resting potential and then is ejected from the channel by electrostatic repulsion allowing conductance of the other ions
How is EPSP measured?
From resting potential higher than Mg2+ blockade in presence or absence of AMPA or NMDA
What does EPSP stand for?
Excitatory Post Synaptic Potential
Describe how neuroplasticity actually occurs
An influx of Ca2+ and Na+ leads to activation of a number of enzymes and other events that cause widespread changes in the postsynaptic cell
What is the link between NMDA receptors and Schizophrenia?
NMDA receptors can be inhibited by PCP (Phencyclidine (angel dust)) and MK801 which produces symptoms that resemble the hallucinations associated with Schizophrenia
What is Glutamate excitotoxicity?
Excessive Ca2+ influx which activates Ca2+-dependent enzymes that degrade proteins, lipids, and nucleic acids
When does Glutamate excitotoxicity occur?
After cardiac arrest, stroke, O2 deficiency, and repeated intense seizures
What is Status epilepticus?
A seizure that lasts longer than 5 minutes or having more than 1 seizure within 5 minutes without enough time to recover
What type of effect do Glutamate receptors have on tissues?
Excitatory
What type of effect do GABA receptors have on tissues?
Inhibitory (brain)
What type of effect do Glycine receptors have on tissues?
Inhibitory (spinal cord and brain stem)
What type of effect do Nicotine receptors have on tissues?
Excitatory at the neuromuscular junction (NMJ) but excitatory or modulatory in the CNS
What type of effect do Serotonin receptors have on tissues?
Excitatory or modulatory
What type of effect do ATP receptors have on tissues?
Excitatory
How do metabotropic receptors work?
They transduce signals into the cells through activation of G-proteins
Describe the mechanism that activates G-proteins
In the resting state, the molecule is bound to GDP but on binding to a ligand, the GDP is switched to GTP causing the molecule to split into a G-alpha and G-beta,gamma
How does the intrinsic GTP-GDP system work?
The breakdown from GTP to GDP switches off the molecule
Describe the structure of a G-protein
~20 alpha subunits including Gs, Gi, and Gq. There are Beta-gamma complexes (5 beta and 12 gamma
What does the beta-gamma complex of a G-protein activate?
K+ channels directly
Which 2 G-protein complexes work on adenylyl cyclase?
Gs and Gi which then inhibits or activates cAMP and the subsequent activation of PKA
Which G-protein complex works on PLC (Phospholipase C)?
Gq. It activates phospholipase C which converts PIP2 into IP3 and DAG. DAG then activates PKC and IP3 releases Ca2+ from internal stores. These two mechanisms activate a Ca2+ dependent enzyme
What does a protein kinase do?
Attaches a phosphate
What does a protein phosphatase do?
Removes a phosphate
What are autoreceptors?
They regulate release of transmitter by modulating it’s synthesis, storage, release, or reuptake. They allow for a feedback loop
What are heteroreceptors?
They regulate synthesis or release of transmitters rather than their own ligands
Give some examples of metabotropic receptors
Group 1,2, and 3 Glutamate, GABAb, Muscarinic acetylcholine, Dopamine, Noradrenaline, Adrenergic, Serotonin, neuropeptide
Which glutamate receptors come under group I?
1 and 5 (Gq)
Which glutamate receptors come under group II?
2 and 3 (Gi)
Which glutamate receptors come under group III?
4, 6, 7, and 8 (Gs)
