Unit 3 Flashcards
Define what are synapses?
Describe the functions of synapse?
Identify and describe anatomical arrangements of synapses?
Identify the differences between electrical and chemical synapses and be able to draw them?
Describe the synaptic events involved in chemical synaptic transmission?
What are synapses and what are the functions of synapses?
Synapse: the region of contact (or near contact) where the neuron transfers information to another cell
Functions: transmit and modulate information between cells
What are Two main types of synapses?
Electrical synapses (gap junction)
• ioniccurrentspreadstonextcellthroughgap junctions
• faster,two-waytransmission&capableof synchronizing groups of neurons
– Chemical synapses
• chemicalmessage(neurotransmitters)
• synapticdelay,one-waytransmissionfroma presynaptic neuron to a postsynaptic neuron
What are the Features of electrical synapses?
Fast transmission (very common in invertebrate for fast withdrawal reflex)
• Vertebrate retina, neocortical interneurons (synchronization signals during early development)
• Nearly always open (specific exceptions such as dark/light modulation in retina), non-selective to ions
• Often bidirectional current flow, but some only pass current in one direction.
• Passage of second messengers, cAMP, Ca2+
Synaptic transmission at Chemical synapses
- Action potential reaches nerve terminals
• 2. voltage-gated Ca2+ channels open
• 3. Ca2+ flows inward triggering release of neurotransmitter
• 4. Neurotransmitter crosses synaptic cleft & binding to ligand-gated receptors 5. which allow ions flow in and
• 6. induce postsynaptic potential change or even
• 7. trigger action potential (nerve impulse) in the
postsynaptic cell
Synaptic delay is ~0.5 msec and One-way information transfer
What is the Synapses?
are functional contact sites between neurons
What are the two main types of Synapses?
electrical and chemical synapses
What is an Electrical Synapses?
Electrical synapses made of connexin proteins which form two halves of connexon that are non- selective for ions and small molecules to pass bidirectionally
What is a Chemical Synapses?
Chemical synapses are composed of presynaptic nerve terminals containing transmitter vesicles, synaptic cleft and postsynaptic receptors
Chemical synaptic transmission
a series of events
What are neurotransmitters?
What are the criteria for being a neurotransmitter?
What are the mechanisms of transmitter removal?
What are the major types of neurotransmitters?
What are the clinical relevance of major transmitters
of Acetylcholine , Serotonin, and Dopamine?
What is a neurotransmitter?
A chemical released by a presynaptic element upon
stimulation that activates postsynaptic receptors
–Housed in presynaptic axon terminal
–Packages in little sacks called vesicles
–Released into synapse with arrival of action potential
–Activates postsynaptic cell –Is cleared from synapse
What are the criteria for a neurotransmitter?
To be a Neurotransmitter, a substance must have
the following properties:
1. A presynaptic cell must have machinery to synthesize or otherwise neurotransmitter is present in the terminal
2. Must be released in sufficient quantities to produce an effect
3. Receptors must exist on post synaptic cell
4. Action must be mimicked by exogenous application of
substance
5. Mechanism for removal exists to stop the postsynaptic effect
Serotonin (5-HT) as a transmitter of clinical relevance
Depression:
Depression: low levels of serotonin in the brain? affect one in 4 to one in 10 people
Neurotransmitters are?
chemicals synthesized, stored,
released in presynaptic neurons which act on their postsynaptic receptors and induced postsynaptic effects. The neurotransmitter is removed from the synaptic site after its action is done.
What are the three major types of conventional transmitters?
Amino acids (Glutamate, GABA, Glycine), Amines (ACh, 5-HT, DA, NE etc.), and Peptides (Substance P, CCK, Dynorphin etc.)
Clinical medicines target to synaptic transmission at all kinds of levels:
precursors, transporters, synthesis, degradation, receptors etc.
Describe several ionotropic and metabotropic receptors and identify key distinctions between them
Know which neurotransmitters activate ionotropic and/or metabotropic receptors
Describe the key steps in signal transduction for G- protein coupled receptors (GPCRs)
What are the Functions of ionotropic receptors?
Mediate Fast synaptic responses
• Essential for rapid communication
• Activation can occur on SUBMILLISECOND time
scale
Always INCREASE membrane conductance
• A) depolarize B) hyperpolarize C) either
What is Excitotoxicity?
excessive presence of glutamate
(Exciting poisons: too much of a good thing)
Ischemia (stroke)
lack of blood → no oxygen and glucose → no pump activity → depolarization → calcium increase → more glutamate release → depolarization (self-reinforcing and spreading)
About metabotropic receptors
They are typically G-protein coupled receptors (GPCRs), or called 7 transmembrane receptors
• Trigger intracellular signaling cascade
• Induce metabolic response
• Mediate slow, wide spread, and long-lasting of responses
What is G-protein?
guanine nucleotide-binding proteins
What is Heterotrimeric
α, β, γ subunits, βγ form a complex
What is Inactive form?
α bound to GDP, no ligand binding to GPCR
What is Active form?
α bound to GTP, after ligand binding to GPCR
G-protein signaling
- Ligand binds to GPCR
- GPCR undergoes conformational change
- αsubunitexchangesitsboundGDPtoGTP
- α subunit dissociates from GPCR and βγ complex
- Both α and βγ regulate target proteins
- Target proteins relay information via 2nd messenger pathways
- GTPhydrolyzedtoGDP
- αsubunitrebindstoβγcomplex
Names of G-protein acting via cAMP-PKA pathways
- Gαs = Gs (stimulatory) increase adenylyl cyclase increase cAMP
increase PKA - Gαi = Gi (inhibitory) decrease adenylyl cyclase decrease cAMP
decrease in PKA
Ligand-gated transmitter receptors:
Ionotropic and metabotropic receptors
Ligand binding to ionotropic receptors do what?
change shape allowing ions to flow through the channels.
Ligand binding to metabotropic receptors (GPCRs) do not…..
And activate what?
have the ion channels. They activate a G-protein that in turn activates secondary messengers (cAMP, cGMP, IP3, DAG, Ca2+), that in turn will activate downstream targets (ion channels, enzyme, transcription factors etc).
The second messengers can do what?
The second messengers can travel throughout the cell and cells in other part of our body and result in a much wider range and long lasting of responses.
What is the key structural feature common to all G-protein coupled receptors (GPCRs)?
How many subunits in the G-protein that is coupled to an GPCR?
Name the enzyme that cleaves a membrane phospholipid to generate IP3 and DAG.
Name the enzyme that catalyzes the formation of cAMP.
Which of the following is the ligand that opens the ligand-gated Ca2+ channel in the endoplasmic reticulum? [DAG; IP3; cAMP; Gβγ complex; Gα]
Name the factor that binds to and activates protein kinase A (PKA).
Name the factor that binds to and activates protein kinase C (PKC).
Which of the following inactivates the alpha subunit of a trimeric G-
protein? [GTP binding; GTP hydrolysis; phosphodiesterase; cholera toxin;
beta-arrestin].
