9. 10. Postsynaptic membrane receptors: ionotropic and metabotropic receptors. Postsynaptic potentials. Flashcards
Types of postsynaptic receptors ( depending on permeability affected directly or indirectly)
Ionotropic
Metabotropic
Properties of ionotropic receptors
When a mediator binds, it leads to DIRECT changes in permeability of given ion channel
Properties of metabotropic receptors
Binding of mediator leads to INDIRECT change in permeability of ion channel, change direction of biochemical reaction, change gene expression
Facilitated by G PROTEINS AND SECOND MESSENGERS which activates KINASES
Mechanism of metabotropic receptors
• specific mediator binding to receptor activates G proteins
• G protein= alpha, beta, gamma subunits
• activates effector protein, adénylate Cyclase
• that generates secind messenger cAMP which generates protein kinase
• kinase changes permeability of channel by PHOSPHORYLATION of amino acid sites on channel
What are the 4 classes of G proteins
Ga s - stimulates production of adenylate cyclase
Ga i- inhibits production of adenylate cyclase
Ga q- stimulates production of PLC
Ga 12/13 - involved in Rho family GTPase signalling
Types of mediators in terms of their synthesis
Low molecular weight compounds
Neuropeptides
Low molecular weight compound synthesis and examples
In presynaptic terminals- they hv rapid effect on postsynaptic membrane
Classical neurotransmitters: Ach, norepinephrine, dopamine, serotonin
Neuropeptide synthesis and examples
In cell body of presynaotic neuron
- axonal transport takes them there
Causes long term changes in permeability of postSM
They change amount of membrane receptors
Gastrin, somatostatin, encephalins, endorphins
Ach synthesis
In the presynaptic endings from acetyl-coenzyme A and choline catalysed by choline acetyl transferase
Secreted by preganglionic nerve fibres of sympathetic and parasympathetic nerve system
Secreted by large pyramidal cells in motor cortex
Secreted from spinal motor neurons innervating skeletal muscles
How is AcH degraded
Degraded in synaptic cleft to acetate and choline by cholineesterase
Can be used by presynaotic ending to make new AcH
What are the types of AcH receptors
Nicotine sensitive N CHOLINORECEPTORS
muscarine sensitive M-CHOLINORECEPTORS
What type of receptors are N-cholineoreceotors
Ionotropic ( so function like ion channels)
Where are N-cholinoreceptors located and how’s it activated
Im autonomic ganglia, neuromuscular junctions, CNS pathways
Binding leads to the entry of Na+ ions and k+ release- leads to excitatory EPSP
What type of receptors are M-cholinoreceptors
Metabotropic (g protein coupled)
The ion channel they regulate is distant from the receptor
M1-5
Effects and location of M1 cholinireceptors
Parietal cells of gastric glands, salivary glands, CNS, sympathetic ganglia
Causes closure of K+ when phospholipase(plc) and IP3 and DAG ( second messengers) bind
Leads to depolarisation- EPSP
Effects and location of M2- cholinoreceptors
In SA node
Causes opening of k+ channels which is directly mediated by class Gi G proteins via beta and gamma subunits
Hyoerpilsrizstion- IPSP
These slow down heart rate caused by parasympathetic nerve system
Effects and location of M3 cholinoreceptord
Bronchial and salivary glands, pupillary constriction and broncho constriction
Lead to depolarisation- EPSP
Effects and location of M5 cholinoreceptors
CNS
clinucal implications not fully explored
Effects and location of M4
CNS
work via Gi and inhibit cAMP
Causes decreased loca motion
Which muscarinuc receptors use Gq that up regulate PLC, IP3 and intracellur Ca2+
Which uses Gi
• M1 M3 M5
• M2 M4
What is the most excitatory mediator in brain
What is most inhibitory mediator in brain
Glutamate
GABA
How is glutamate and GABA synthesised
Glutamate: in kerbs cycle amination of a-ketoglutsrate
GABA- decarboxylation of glutamate ( glutamate y-aminobutyric acid)
What are the type of glutamate recpetors
Ionotropic= NMDA and AMPA
Metabotropic= group 1,2,3
How are NMDA and AMPA activated by glutamate
- The glutamate released by presynaptic ending binds to both receptors
- It ACTIVATES AMPA so depolarization-Na enter K exit
- Depolarization reaches NMDA and causes release of Mg2+ (before it blocked channel) which ACTIVATES NMDA leading to influx of Na+ and Ca 2+ and K+ exit
- Therefore for NMDA binding of glutamate required AND depolarization of membrane required
Difference between Metabotropic glutamate receptors and ionotropic
- Slower synaptic transmossion
- BUT can amplify repeated weak signals due to cascade responses
- Both receptors involved in learning and memory
- in pre- and post-synaptic
neurons of the hippocampus, cerebellum, and the cerebral cortex,
What does GABA stand for and synthesis
γ-aminobutyric acid
decarboxylation of glutamate in Krebs cycle
Major inhibitory neurotransmitter in brain
Tyoes of GABA receptors
GABA a GABAc = ionotropic
GABAb = metabotropic
GABAa characteristics
Selective for Cl- ion and causes inhibitory post synaptic potential
Benzodiazepines and barbiturates facilitate this receptor and act as anticonvulsants and sedatives
GABAc characteristics
Also a Cl- channel BUT doesnt have drug binding site like a
Leads to IPSP
GABAb characteristics
Opens K+ channels
Activated by G protein Gi via b and y subunits
Leads to IPSP
What are the function of the GABA receptors
- reduce neuronal excitability by inhibition of neuron to
neuron transmission. - If GABA binds to many neurons, this causes sedation
- GABAergic neurons are present in hippocampus, thalamus, basal ganglia,
hypothalamus, and brainstem.
What are some biogenic amine neurotransmitter
Catecholamines ( dopamine, epinephrine, norepinephrine
Serotonin
If damaged which neurons cause parkinsons disease
Dopamine neurons
What does serotonin regulate and what happens if theres too much
Mood apetite sleep rhythms, digestion, blood clotting
shivering and diarrhea to
severe like, muscle rigidity, fever and seizures.
What are the mechanisms of termination of neurotransmitter action?
Diffusion out of synaptic cleft.
Enzymatic degradation into synaptic cleft.
Going back to the presynaptic end.
Examples of second messengers
cAMP, cGMP, IP3 , DAG
