Podcast
Questions and Answers
What role do protein kinases play in the signal transduction process?
What role do protein kinases play in the signal transduction process?
Which of the following best describes the concept of third messengers in gene activation?
Which of the following best describes the concept of third messengers in gene activation?
What structural feature characterizes G protein-coupled receptors (GPCRs)?
What structural feature characterizes G protein-coupled receptors (GPCRs)?
Which system or receptor is NOT mentioned as constitutively active among GPCRs?
Which system or receptor is NOT mentioned as constitutively active among GPCRs?
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Which statement about NF-kB is correct?
Which statement about NF-kB is correct?
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What is the primary function of a chemical synapse?
What is the primary function of a chemical synapse?
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Which neurotransmitter is NOT listed as part of the gliotransmitters in tripartite synapses?
Which neurotransmitter is NOT listed as part of the gliotransmitters in tripartite synapses?
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Which of the following correctly describes step 3 of neurotransmission?
Which of the following correctly describes step 3 of neurotransmission?
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Who contributed to the discovery of the chemical nature of synapses?
Who contributed to the discovery of the chemical nature of synapses?
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What accurately describes the role of astrocytes in synaptic transmission?
What accurately describes the role of astrocytes in synaptic transmission?
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In what format does neurotransmission occur across chemical synapses?
In what format does neurotransmission occur across chemical synapses?
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Which of the following is a potential outcome after a neurotransmitter binds to a postsynaptic receptor?
Which of the following is a potential outcome after a neurotransmitter binds to a postsynaptic receptor?
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Which neurotransmitter is synthesized from choline found in the diet?
Which neurotransmitter is synthesized from choline found in the diet?
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What characterizes the release of neuropeptides compared to other neurotransmitters?
What characterizes the release of neuropeptides compared to other neurotransmitters?
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How do lipid neurotransmitters like endocannabinoids act on receptors?
How do lipid neurotransmitters like endocannabinoids act on receptors?
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Which of the following is classified as a gaseous neurotransmitter?
Which of the following is classified as a gaseous neurotransmitter?
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What best describes the duration of effects for neuropeptides?
What best describes the duration of effects for neuropeptides?
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Which neurotransmitter is NOT classified as a catecholamine?
Which neurotransmitter is NOT classified as a catecholamine?
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Where are neuropeptides primarily synthesized in the neuron?
Where are neuropeptides primarily synthesized in the neuron?
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Which of the following neurotransmitters binds to CB1 and CB2 receptors?
Which of the following neurotransmitters binds to CB1 and CB2 receptors?
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What distinguishes ion transmitters like zinc (Zn2+) from traditional neurotransmitters?
What distinguishes ion transmitters like zinc (Zn2+) from traditional neurotransmitters?
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Which receptor type predominantly uses G-protein coupled pathways?
Which receptor type predominantly uses G-protein coupled pathways?
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What is the primary effector enzyme associated with the cAMP signaling pathway?
What is the primary effector enzyme associated with the cAMP signaling pathway?
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Which signaling pathway is associated with the formation of IP3 and DAG?
Which signaling pathway is associated with the formation of IP3 and DAG?
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Which secondary effector is associated with the phosphoinositol pathway?
Which secondary effector is associated with the phosphoinositol pathway?
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In the signaling pathways associated with neurotransmitters, which of the following first messengers activates the phosphoinositol system?
In the signaling pathways associated with neurotransmitters, which of the following first messengers activates the phosphoinositol system?
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Which G-protein coupled receptor type is primarily linked to changes in potassium conductance?
Which G-protein coupled receptor type is primarily linked to changes in potassium conductance?
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What is the role of IP3 in G-protein signaling pathways?
What is the role of IP3 in G-protein signaling pathways?
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Which of the following second messengers is produced from the activation of phospholipase C?
Which of the following second messengers is produced from the activation of phospholipase C?
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What common property do GPCRs share regarding ion channels?
What common property do GPCRs share regarding ion channels?
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Which hormone is associated with the activation of the cAMP signaling pathway?
Which hormone is associated with the activation of the cAMP signaling pathway?
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What is the role of vesicles in neurotransmitter transport?
What is the role of vesicles in neurotransmitter transport?
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What determines the effect of a neurotransmitter on the postsynaptic cell?
What determines the effect of a neurotransmitter on the postsynaptic cell?
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Which channels are considered active channels?
Which channels are considered active channels?
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What characterizes metabotropic receptors in neurotransmission?
What characterizes metabotropic receptors in neurotransmission?
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What effect does ligand-induced desensitization have on receptor function?
What effect does ligand-induced desensitization have on receptor function?
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Which type of neurotransmission is characterized as very fast, occurring in a few milliseconds?
Which type of neurotransmission is characterized as very fast, occurring in a few milliseconds?
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What is the result of up-regulation in the absence of a ligand?
What is the result of up-regulation in the absence of a ligand?
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Which of the following describes the function of cAMP as a second messenger?
Which of the following describes the function of cAMP as a second messenger?
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What type of receptor is typically activated by neurotransmitters that also influences second messenger systems?
What type of receptor is typically activated by neurotransmitters that also influences second messenger systems?
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Which of the following is NOT a class of gated channels?
Which of the following is NOT a class of gated channels?
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Study Notes
Synapses
- Neurons communicate by transmitting chemicals at junctions called "synapses"
- Charles Scott Sherrington coined the term in 1906 to describe the specialized gap between neurons
- Sherrington's discovery was a significant scientific advancement
- Santiago Ramón y Cajal hypothesized that contact points (later termed synapses) were crucial for brain information processing
- Sherrington's work identified synaptic delay and properties of summation (spatial and temporal)
- Reflexes are slower than axon conduction showing the existence of synaptic delay.
- Summation involves cumulative effects of excitatory (EPSPs) and inhibitory (IPSPs) signals to generate neural impulses.
Summary of the Lecture
- Synaptic concept, types, and physiology
- Neurotransmitters and their classes
- Ionotropic/metabotropic receptors
- Variations in signal transduction and structure
Types of Synapses
- Electrical—current flows through gap junctions.
- Chemical—neurotransmitters are involved.
- Electrical synapses are faster than chemical ones for synchronized neuronal firing.
Electrical Synapses
- A few special-purpose synapses use electrical signals.
- Faster than chemical transmissions.
- Direct contact between neuron membranes via gap junction.
- Depolarization in both neurons acts as if they were one.
- Used where speed is important (e.g., rhythmic activities).
Chemical Synapse
- Most synapses in mammals are chemical.
- Neurotransmitters are released from presynaptic neuron to postsynaptic neuron to excite or inhibit it.
- Otto Loewi's experiments demonstrated the chemical nature of these junctions.
Anatomy of the Chemical Synapse
- Presynaptic membrane—encloses molecules that transmit chemical messages.
- Synaptic cleft—small space between presynaptic and postsynaptic terminals.
- Postsynaptic membrane—contains receptor molecules that receive chemical messages.
- Microtubules—transport substances to the axon terminal.
- Mitochondria—organelles providing energy.
- Synaptic vesicles—round granules that contain neurotransmitters.
- Storage granules—large compartments that hold synaptic vesicles.
- Neurotransmitter channel—site where a neurotransmitter molecule binds
Tripartite synapses
- Astrocytes are key in regulating the synapse and synaptic neurotransmitter levels.
- Astrocyte excitability is essential for various synaptic functions.
- Gliotransmitters (e.g., glutamate) are involved.
"Quad-partite" synapses
- Microglia are crucial for synaptic plasticity.
- This "quad-partite" structure further refines models of synapse function.
Neurotransmission in 5 Steps
- The neurotransmitter is synthesized inside the neuron.
- It's packaged and stored in vesicles at the axon terminal.
- Released into the synaptic cleft in response to an action potential.
- Binds to and activates receptors on the postsynaptic membrane
- Degraded or removed preventing continuous interactions.
Steps 1 and 2: Neurotransmitter Synthesis, Packaging, and Storage
- Neurotransmitters are synthesized in the axon terminal (small-molecule) or in the cell body (peptide transmitters).
- Building blocks are pumped into the terminals.
- Packed into the vesicles.
- Transported to the axon terminal.
Step 3: Neurotransmitter Release
- Action potential opens voltage-sensitive calcium (Ca2+) channels.
- Calcium enters the axon terminal activating a complex with other proteins.
- Vesicles fuse with the presynaptic membrane and release their contents.
Step 4: Receptor Site Activation
- Neurotransmitter diffuses across the synaptic cleft and activates receptors on the postsynaptic membrane.
- Receptor properties determine the nature of the effect on the postsynaptic neuron.
Steps 4: Receptor Site Activation
- Depolarization (EPSP) or hyperpolarization (IPSP).
- Initiate other chemical reactions to modify effect.
- Interaction with receptors on the presynaptic membrane (autoreceptors).
Autoreceptors - Heteroreceptors - Postsynaptic receptors
- Autoreceptors detect released neurotransmitter and regulate further synthesis and release,
- providing feedback control.
- Heteroreceptors respond to other neurotransmitters released by other neurons.
Spontaneous Firing Rate
- EPSPs: Increase the number of action potentials above the spontaneous firing rate.
- IPSPs: Decrease the number of action potentials below the spontaneous firing rate.
Inactivation and Reuptake of Neurotransmitters
- Diffusion: some neurotransmitter diffuses away from the synapse.
- Degradation: Enzymes in the synaptic cleft break down the neurotransmitter.
- Reuptake: Presynaptic neuron brings back neurotransmitter molecules for re-use.
- Astrocyte Uptake: astrocytes absorb neurotransmitter and may store it for reuse.
Classes of Neurotransmitters
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Amino acids
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Monoamines
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Indoleamines
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Catecholamines
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Peptides
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Purines
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Gasses
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Fatty Acids
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Neurotransmitters often have multiple effects dependent on the receptor type or subtype the transmitter binds to.
Synthesis of Neurotransmitters
- Neurons synthesize neurotransmitters and other chemicals from chemical components obtained from the diet.
- Specific neurotransmitter precursors are needed dependent on the neurotransmitter being created.
Pathways in the Synthesis of Transmitters
- Specific pathways exist to synthesize certain transmitters in the body.
- Necessary precursors are required to synthesize the required transmitter.
Neuropeptides
- Metabotropic effects utilize multiple neurotransmitters.
- Releasing peptide triggers same neuropeptide release in other neurons.
- Diffuse widely and affects multiple neurons.
- Release requires repeated stimulation.
Lipid Transmitters
- Endocannabinoids are lipid neurotransmitters synthesized in the postsynaptic membrane to act on receptors at the presynaptic membrane.
- Include Anandamide and 2-AG.
- Bind to CB1 and CB2 receptors.
- Can also be derived from arachidonic acid.
Gaseous and Ion Transmitters
- Gasses (nitric oxide, etc.) are not stored in vesicles and readily cross membranes.
- Zinc is considered a transmitter actively transported into vesicles, often with other transmitters.
Activating Receptors of the Postsynaptic Cell
- Receptor activation by a neurotransmitter determines the effect.
- Transmitter-gated channels controlled by a neurotransmitter.
Post-Synaptic Effects
- Fast synaptic transmission (milliseconds).
- Slow synaptic transmission (tenths of a second to hours).
- Very slow synaptic transmission (days to years).
- Modulation affects overall neural response.
Ionotropic Receptors
- Fast transmitter effects.
- Receptors combined as channels.
- Act quickly (milliseconds) and rely on glutamate/GABA.
G protein-coupled receptors (GPCRs)
- Metabotropic receptors, linked to G-Proteins.
- Slower but longer-lasting effects.
- Utilize second messenger systems.
- Trigger changes in ion channel activity.
- Involved in a wide range of behaviors
lonotropic vs Metabotropic- Structure
- Ionotropic receptors have a channel-forming domain.
- Metabotropic receptors are large, membrane embedded protein complexes.
Classes of Ionotropic Receptors
- Glutamate Receptors (AMPA, NMDA, Kainate)
- GABA Receptors (GABAA)
- Glycine Receptors
- Acetylcholine Receptors (nACh)
- Serotonin Receptors (5-HT3)
- Purine Receptors
Classes of Metabotropic Receptors
- Glutamate Receptors (mGluR)
- GABA B receptors
- Dopamine receptors
- Norepinephrine/Epinephrine receptors
- Histamine receptor
- Serotonin receptors
- Other neurotransmitter receptors and specific subtypes
Neurotransmitters/Neuromodulators
- Summarizes types of transmitters, their receptors, important features.
Negative Feedback in the Control of Thyroid Hormones
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The hypothalamus regulates thyroid hormone levels thru a negative feedback loop.
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Thyroid hormone levels affect TSH-releasing hormone production via a negative feedback pathway.
Maintaining Hormonal Levels
- Hypothalamus controls hormone levels via negative feedback mechanisms
- Hormones like TSH releasing hormone and thyroid hormones exhibit negative feedback regulation.
Some Major Events in Transmission at a Synapse
- Key elements and steps of synaptic transmission are summarized.
- Events such as vesicle synthesis, neurotransmitter release, re-uptake, and feedback are described
Storage of Transmitters
- Vesicles store neurotransmitters for release.
- MAO breaks down excess neurotranmitters.
- Exocytosis releases neurotransmitters into the synaptic cleft triggered by action potentials.
Release and Diffusion of Transmitters
- Neurotransmitter release and crossing the synaptic cleft is very fast.
- Most neurons release at least 2 or more types of neurotransmitters.
- Neurons can also respond to multiple transmitters beyond the ones they release.
A neurotransmitter can affect a postsynaptic cell via two types of receptor proteins:
- Ionotropic receptors combine receptor binding and channel functions.
- Metabotropic receptors are separate entities where receptor binding initiates a sequence of metabolic steps.
Architecture of metabotropic receptors
- Metabotropic receptors have a complex structure with multiple transmembrane domains.
- Neurotransmitter binding site
- G protein binding sites
Modulation
- Synaptic activation of G protein-coupled receptors often modifies the effects of other synapses instead of directly evoking EPSPs or IPSPs.
G protein-coupled receptors (GPCRs)
- Regulate potassium conductance, adenylyl cyclase activity, and phosphoinositide breakdown and protein kinase activation.
- May have a constitutive activity.
Pathway of IP3 and DAG
- Signaling cascade where these second messengers initiate various cellular responses.
- IP3 - activates calcium channels in the endoplasmic reticulum.
Different second messengers, different effects
- Lists the different second messengers (e.g., cAMP, phosphoinositides)
- Shows their associated neurotransmitter and receptor types.
Regulation of gene expression
- NF-kB a transcription factor
- CREB, cellular immediate-early genes (c-fos, fosB, c-jun, junB) are involved in gene regulation.
- These are third messengers involved in gene expression.
Signal transduction to the nucleus
- A summary of how neurotransmitters influence gene expression via signaling pathways.
- The process links neurotransmitter binding to activating genes inside the nucleus.
Constitutive activity of GPCRs
- Detailing the inherent activity of a receptor even without a ligand.
GPCR dimers and cross-talk
- G protein-coupled receptors can form homo- or heterodimers.
Drugs that Act by Binding to Receptors
- Hallucinogenic drugs mimic serotonin activity, stimulating serotonin 2A receptors.
- Certain drugs act by stimulating different receptor subtypes.
Opiate Drugs and Endorphins
- Opiates bind to the same receptors as endorphins, produced by the brain.
Hormones
- Secreted by glands and travel via the blood, altering organ activity.
Location of Some Major Endocrine Glands
- Shows the approximate locations of major endocrine glands in the human body.
A Selective List of Hormones
- Comprehensive list of hormones alongside their roles and effects.
Proteins and Peptides
- Proteins and peptides are important components of the endocrine system.
- They influence other tissues via second messenger systems.
The Pituitary Gland and the Hypothalamus
- The relationship and structure of the hypothalamus and pituitary.
- Describing their roles in controlling hormone release.
Location of the Hypothalamus and Pituitary Gland in the Human Brain
- Illustrates locations in the brain using a diagram.
Pituitary Hormones
- Diagram illustrating the arrangement and production of key hormones in the pituitary.
Neurotransmitter-containing vesicles
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Description
Test your knowledge on the critical roles of protein kinases, GPCRs, and neurotransmitters in the signal transduction process and synaptic transmission. This quiz covers various aspects of neurotransmission, including chemical synapses, third messengers, and the contributions of astrocytes. Perfect for students studying cellular communication and neurobiology.
