Transcript 9ReceptorTypes1

Ionotropic and Metabotropic
Receptors
Recall the 2 Kinds of Synapses?
Electrical
• 2 neurons linked together
by gap junctions
• Function in nervous
system:
- rapid communication
- bidirectional
communication
- excitation/inhibition at
the same synapse
• Some between neurons
and glia cells
•
•
•
•
•
Chemical
Signal transduction
Excitatory
Inhibitory
Slower communication
Unidirectional
communication
Recall where chemical
synapses are found?
Recall the Chemical Synapse?
Communication
Across a Synapse
1. Action Potential
2. Voltage-gated Ca
channels open
3. Ca triggers exocytosis
4. Nt diffuses and binds to
receptor
5. Response in cell
Response is terminated by
removing nt from
synaptic cleft
6. Degradation
7. Reuptake
8. Diffusion
Signal Transduction at Synapses
• Rate of the response is due to the mechanism
by which the signal is received and transferred
at the plasma membrane.
• Fast responses at ionotropic receptors
(channel-linked).
• Slow responses at metabotropic receptors
(G-protein-linked).
Ionotropic Receptors
• The receptor is a ligand-gated ion channel.
• Ligand binding directly opens ion channel.
• Fast action, short latency between nt binding
and response.
• Response is brief.
Ionotropic Receptors
• 5 subunits form the pore through
the membrane.
• Binding of ligand opens the pore.
• Ions flow into or out of the cell.
• Produces EPSP or IPSP
(depending on the ion channel).
• Rapid desensitization (loss of
activity) if continuously exposed
to nt.
• Limits postsynaptic responding
when presynaptic neurons are
highly active for a period of time.
Ionotropic Receptors
Sensitization
High
Ion Flow
Low
Time, ms, in exposure to neurotransmitter
Ionotropic Receptors
• Can have multiple
binding sites for various
neuromodulators.
• Can enhance or inhibit
binding of endogenous
ligands.
• Are good targets for
drugs.
Fast Responses at Ionotropic
Receptors
Metabotropic Receptors
• Most common type of
receptor.
• Coupled to G protein.
• No direct control of ion
channels.
• Second messengers.
Metabotropic Receptors
• Single subunit with 7 transmembrane spanning
domains.
• Highly conserved across the “receptor
superfamily”.
• Ligand binds in cleft on external face.
• Ligand binding activates G protein
• G protein activate various effectors.
• Sometimes the effectors are the ion channels.
β-adrenergic
receptor
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Slow Responses at Metabotropic
Receptors: Direct G-Protein Coupling
Slow Responses at Metabotropic
Receptors: Second Messenger Coupling
Postsynaptic Potential
• Change in membrane potential in response to
neurotransmitter binding to receptor.
• Can be excitatory or inhibitory:
- Excitatory: likely to elicit action potential:
Deporalization
-Inhibitory: less likely to elicit action potential:
Hypoerpolarization
Membrane Stabilization
Excitatory Synapses
• Depolarize postsynaptic cell
-Brings membrane potential closer to Threshold by
opening or closing ion channels.
• Channels affected are:
- Open Na channels
- Close K channels
- Open channels that are equally permeable to Na and
K
Causes depolarization because of the stronger force of Na
to flow into the cell
• Depolarization = EPSP (excitatory postsynaptic
potential)
Fast EPSPs
Slow EPSPs
EPSPs are Graded Potentials
• Higher freq of APs (presynaptic)
• More neurotransmitter released (presynaptic)
• More neurotransmitter binds to receptors to open
(or close) channels
• Greater increase (or decrease) ion permeability
• Greater (or lesser) ion flux
• Greater depolarization
Inhibitory Synapses
• Neurotransmitter binds to receptor.
• Channels for either K or Cl open 
hyperpolarizes the cell.
• If K channels open, then…
 K moves out  IPSP
(inhibitory postsynaptic potential)
• If Cl channels open, then either…
 Cl moves in  IPSP
 Cl stabilizes membrane potential.
Fast Inhibitory
Synapses Involving
K Channels
IPSPs are Grade Potentials
• Higher freq of APs (presynaptic)
• More neurotransmitter released (presynaptic)
• More neurotransmitter binds to receptors to open (or
close) channels
• Greater increase (or decrease) ion permeability
• Greater (or lesser) ion flux
• Greater depolarization
Neural Integration
• Divergence/convergence
• Summation
• The summing of input from various synapses
at the axon hillock of the postsynaptic neuron
to determine whether the neuron will
generate action potentials
Divergence
Convergence
Convergence of Input as a Factor in
Summation
Temporal Summation from the same
Synapse
Spatial Summation from Different
Synapses
Neurotransmitters
•
•
•
•
•
Acetylcholine
Biogenic Amines
Amino Acid Neurotransmitters
Neuropeptides
Autonomic Nervous Sysntem
Acetylcholine
• Found in the CNS and PNS
• Most abundant neurotransmitter in PNS.
• Synthesis
- Acetyl CoA + choline  acetylcholine +CoA
- Synthesized in cytoplasm of axon terminal
- Biosynthetic enzyme: choline acetyltransferase (CAT)
• Breakdown
- Acetylcholine  acetate + choline
- Degradation occurs in synaptic cleft
- Degradative enzyme: acetylcholinesterase (AchE)
Cholinergic
Synapse
Cholinergic Receptors
• Nicotinic
- Ionotropic
- Found mostly in the skeletal muscle
- Some found in the CNS
• Muscarinic
- Metabotropic
- Found mostly in the CNS
Actions at Nicotinic Cholinergic
Receptors
Actions at Muscarinic Cholinergic
Receptors
Biogenic Amines
• Derived from amino acids
• Catecholamines – derived from tyrosine
- Dopamine
- Norepinephrine (noradrenaline)
- Epinephrine (adrenaline)
• Norepineprine and epinephrine bind adrenergic
receptors
- Alpha and beta adrenergic receptors
- Slow responses at all adrenergic receptors
• Adrenergic receptors are G-protein-coupled
• Generally linked to second messengers
Dopamine
• Category: biogenic amine
• Postsynaptic effect: Excitatory or inhibitory
Fig. 6.11
Dopamine Receptors
• Large diversity of metabotropic dopamine
receptors (at least 6).
• Bound by many antipsychotic drugs
Kandel, 2000
Norepinephrine
• Category: biogenic amine
• Formed from dopamine
• also in PNS
– sympathetic NS
Norepinephrine Receptors
• Effect depends on receptor bound
– α-receptors
α1- vs. α2-receptors (see next slide)
– ß-receptors
Silverthorn 2004
Receptors can be Located Presynaptically too –
This will determine their effect
Presynaptic GABAB receptor actions
Isaacson, J
Epinephrine
• Category: biogenic amine
• synthesized from norepinephrine
• Effect depends on receptor bound
– α-receptors
– ß-receptors
Histamine
• Category: biogenic amine
• Postsynaptic effect: Excitatory
Fig. 6-12
Histamine effects
•
•
•
•
Receptors are all G-protein coupled
In brain, affects arousal and attention
In periphery affects inflamation, vasodilation.
Why do some cold medicines make you
sleepy? (good exam question).
Serotonin (5-HT)
Category: Biogenic amines
• Postsynaptic effect: Excitatory
Serotonin effects
• Involved in sleep/wakefulness cycle
• Most receptors are metabotropic, but one
group are ionotropic.
• Why does turkey make you sleepy?
• SSRI and depression
Amino Acid Neurotransmitters
• Amino acid neurotransmitters at excitatory
Synapses: glutamate
• Amino acid neurotransmitters at inhibitory
Synapses: GABA (gamma-amino butyric acid)
• Category: small-molecule
• Glutaminergic neurons
• Postsynaptic effect:
depends
• Very important in CNS
• Synthesized from
glutamine from glia
Glutamate
Fig. 6.6
Glutamate Receptors
• Ionotropic
– NMDA
• late EPSP
• Glycine & Mg2+ dependent
– AMPA
• early EPSP
– kainate
• early EPSP
• Metabotropic
Kandel 2000
GABA (γ-aminobutyric acid)
• Category: small-molecule
• GABAergic neurons
• Postsynaptic effect:
Inhibitory
• Made from glucose
Fig. 6.8
GABA Receptors
• GABAA – Ionotropic
– gates Cl- channel
• GABAB – Metabotropic
– gates K+ channel
Fig. 6.9
Neuropeptides
• Short chains of amino acids
• E.G., endogenous opiates
- endorphins – found in the brain,
morphine-like
- Vasopressin – Anjtidiuretic hormone
(ADH) – found in the posterior
pituitary
Autonomic Nervous System (ANS)
• Both branches of the ANS innervate most
effector organs
• Primary function – regulate organs to
maintain homeostasis
• Parasympathetic and sympathetic activities
tend to oppose each other
- Parasympathetic Nervous system – rest
- Sympathetic nervous system – fight or flight
response
Autonomic Pathways
Neurotransmitters and their Receptors in
the ANS