Neurotransmission Mechanisms
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Questions and Answers

Which mechanism primarily involves transporter proteins embedded in the cell membrane to remove neurotransmitters from the synaptic cleft?

  • Direct inhibition of neurotransmitter release
  • Glial cell uptake
  • Enzymatic breakdown
  • Reuptake (correct)

A drug that inhibits acetylcholinesterase would have which effect on neurotransmission involving acetylcholine (ACh)?

  • Shorten the duration of ACh's effect in the synapse
  • Decrease the amount of ACh released into the synapse
  • Prevent ACh from binding to its receptors
  • Prolong the duration of ACh's effect in the synapse (correct)

If astrocytes surrounding a synapse are damaged, which neurotransmitter's concentration in the synaptic cleft would likely be most affected?

  • Glutamate (correct)
  • Monoamines
  • Acetylcholine
  • Glycine

Selective Serotonin Reuptake Inhibitors (SSRIs) are a class of drugs that block reuptake mechanisms. What is the primary effect of SSRIs on serotonin neurotransmission?

<p>Increased serotonin levels in the synaptic cleft (B)</p> Signup and view all the answers

Which of the following best describes the mechanism by which certain psychoactive drugs affect neurotransmission, based on the content?

<p>By blocking reuptake mechanisms, thus prolonging neurotransmitter action (D)</p> Signup and view all the answers

Which of the following accurately describes the function of protein kinases?

<p>They alter protein structure and function by adding phosphate groups. (B)</p> Signup and view all the answers

Neurotrophic factors are MOST important for which physiological process?

<p>Neuronal development and survival (B)</p> Signup and view all the answers

What is the primary characteristic of ionotropic receptors that distinguishes them from other types of receptors?

<p>They directly form an ion channel upon ligand binding. (A)</p> Signup and view all the answers

How does the stimulation of trkB receptors relate to the function of BDNF?

<p>BDNF directly stimulates trkB receptor activation. (B)</p> Signup and view all the answers

Based on the information, what receptor does Neurotrophin-3 (NT-3) primarily activate?

<p>trkC receptor (D)</p> Signup and view all the answers

Ionotropic receptors are composed of multiple subunits, what is a common feature that arises due to this characteristic?

<p>Variations in function due to subunit composition (A)</p> Signup and view all the answers

A researcher is studying the effects of a novel compound on neuronal survival. Which factor would be MOST relevant to investigate, considering its known role in supporting neurons?

<p>Concentration of Brain-Derived Neurotrophic Factor (BDNF) (B)</p> Signup and view all the answers

A scientist is looking for a way to selectively activate trkC receptors in a neuronal culture. Which of the following neurotrophins would be MOST appropriate for this purpose?

<p>Neurotrophin-3 (NT-3) (D)</p> Signup and view all the answers

How does cholera toxin lead to persistent activation of G proteins?

<p>By blocking the GTPase activity of the G protein, preventing its inactivation. (A)</p> Signup and view all the answers

Which of the following describes the mechanism of action of pertussis toxin on G proteins?

<p>It prevents G proteins from interacting with receptors, effectively inactivating the signaling pathway. (B)</p> Signup and view all the answers

The direct interaction between G proteins and K+ channels (specifically Go) in somatodendritic regions typically leads to which cellular effect?

<p>Hyperpolarization, decreasing the likelihood of action potential firing. (B)</p> Signup and view all the answers

If a researcher is studying the structure and function of G proteins and aims to selectively inhibit G protein signaling, which toxin would be most appropriate to use?

<p>Pertussis toxin, because it prevents G proteins from interacting with receptors. (C)</p> Signup and view all the answers

Which of the effectors below are directly linked to G-proteins, where applicable?

<p>Potassium channels (Go). (D)</p> Signup and view all the answers

How do calcium pumps maintain resting cytoplasmic $Ca^{2+}$ concentrations?

<p>By transporting $Ca^{2+}$ out of the cell or into the endoplasmic reticulum. (A)</p> Signup and view all the answers

What is the primary role of Calmodulin after binding with $Ca^{2+}$?

<p>To regulate a number of intracellular proteins, influencing various cellular processes. (B)</p> Signup and view all the answers

What is the immediate consequence of activating ionotropic receptors such as the NMDA receptor?

<p>A rapid elevation in cytosplasmic $Ca^{2+}$ levels. (A)</p> Signup and view all the answers

What would be the likely effect of a drug that blocks IMP3?

<p>Decreased $Ca^{2+}$ release from the endoplasmic reticulum. (C)</p> Signup and view all the answers

Which of the following represents the correct order of events in a signaling cascade initiated by a neurotransmitter binding to a G-protein coupled receptor?

<p>Neurotransmitter binding -&gt; activation of G-protein -&gt; activation of second messenger -&gt; activation of kinases -&gt; phosphorylation of transcription factors (D)</p> Signup and view all the answers

Which of the following components are typically found in ionotropic receptors?

<p>Neurotransmitter binding sites, an intrinsic ion channel, and allosteric sites. (D)</p> Signup and view all the answers

How does the ion selectivity of an ionotropic receptor affect its function?

<p>Ion selectivity dictates whether receptor activation leads to excitation or inhibition. (C)</p> Signup and view all the answers

What is the primary effect of $Cl^-$ influx through $GABA_A$ receptors on the post-synaptic neuron?

<p>Hyperpolarization and inhibition. (C)</p> Signup and view all the answers

Which of the following is a distinguishing characteristic of ionotropic receptors compared to other types of receptors?

<p>They directly gate ion channels. (A)</p> Signup and view all the answers

What role do allosteric sites play in the function of ionotropic receptors?

<p>They modulate the receptor's response to neurotransmitter binding. (A)</p> Signup and view all the answers

How many subunits constitute a nicotinic acetylcholine ($ACh$) receptor?

<p>5 (D)</p> Signup and view all the answers

What is the primary effect of calcium $Ca^{2+}$ influx through NMDA receptors?

<p>Acting as a second messenger to initiate intracellular signaling cascades. (D)</p> Signup and view all the answers

Which of the following best describes the speed of ionotropic receptors compared to other receptor types?

<p>Faster, because they directly gate ion channels (C)</p> Signup and view all the answers

A scientist is studying a newly discovered receptor. Initial findings show that receptor activation leads to an amplified intracellular signaling cascade via an intermediary protein. Which type of receptor is most likely involved?

<p>Metabotropic receptor (C)</p> Signup and view all the answers

Which of the following statements accurately describes the composition and function of G proteins?

<p>G proteins are composed of three subunits (α, β, and γ) and are regulated by the binding of guanine nucleotides. (D)</p> Signup and view all the answers

A researcher observes that a specific G protein subtype activates adenylyl cyclase. Based on the information, which G protein subtype is most likely involved?

<p>Gs (C)</p> Signup and view all the answers

What determines if the G-protein is active or not?

<p>The binding of guanyl nucleotides (D)</p> Signup and view all the answers

What is the dual mechanism of action for G-Protein Coupled Receptors?

<p>Act on ion-channels with the g-protein and activate an effector enzyme with the g-protein (C)</p> Signup and view all the answers

A new drug is designed to target the α subunit of G proteins to modulate downstream signaling pathways. What is a crucial structural feature of this subunit that makes it a suitable target?

<p>It contains a guanyl nucleotide binding site to regulate G protein activity. (C)</p> Signup and view all the answers

A researcher is studying the effect of a neurotransmitter on a neuron. They notice that when the neurotransmitter binds to its receptor, the neuron's membrane potential becomes more negative, making it less likely to fire an action potential. Which type of receptor activation is most likely responsible for this effect?

<p>Activation of metabotropic receptors coupled to Gi proteins. (D)</p> Signup and view all the answers

Which of the following is NOT a characteristic of metabotropic receptors?

<p>They directly form an ion channel within the receptor structure. (A)</p> Signup and view all the answers

Flashcards

Inhibition of NT release

Mechanism that directly reduces the release of neurotransmitters at synapses.

Enzymatic breakdown

Process where enzymes like acetylcholinesterase deactivate neurotransmitters such as ACh.

Reuptake

The process where neurotransmitters are reabsorbed by transporter proteins in the presynaptic neuron.

Glial cells and NT inactivation

Supporting cells that help inactivate neurotransmitters, such as astrocytes taking up glutamate.

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SSRIs and neurotransmission

Selective serotonin reuptake inhibitors prolong the action of serotonin by blocking its reuptake.

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BDNF

Brain-derived neurotrophic factor, essential for neuronal survival and growth.

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Neurotrophins

Proteins that promote survival, development, and function of neurons; include BDNF, NT-3, and NT-4.

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trkB receptor

A receptor that binds BDNF, important for neuronal signaling and growth.

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Phosphorylation

The addition of phosphate groups to proteins, changing their function.

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Protein kinase

An enzyme that catalyzes phosphorylation of proteins, modifying their activity.

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Ionotropic receptors

Receptors that are ligand-gated ion channels, allowing ions to flow through when activated.

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Receptor heterogeneity

Variability in the subunit composition of receptors, affecting their function and properties.

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Ligand-gated channels

Channels that open in response to binding of a specific molecule (ligand).

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Vibrio Cholerae Toxin

A toxin that activates G-proteins by blocking GTPase activity, causing diarrhea.

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Bordetella Pertussis Toxin

A toxin that inhibits G protein interaction with receptors, leading to whooping cough.

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G-Protein Activation

Process where G proteins are activated through interaction with specific toxins, affecting signal transduction.

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Ion Channels

Proteins that allow ions to pass through the membrane, influenced by G proteins and toxins.

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Second Messenger

Molecules that relay signals received by cell surface receptors to target molecules inside the cell.

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Neurotransmitter binding site

The specific area on a receptor where neurotransmitters attach.

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Intrinsic ion channel

A part of the receptor that allows certain ions to pass through upon activation.

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Ion selectivity

The property that determines which ions can pass through the receptor channel.

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Nicotinic receptor

A type of ionotropic receptor that responds to acetylcholine (ACh).

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NMDA receptor

A specific receptor that allows Ca2+ ions to enter, involved in memory processes.

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GABAA receptor

An ionotropic receptor that primarily allows Cl- to flow, inhibiting neural activity.

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Subunits of receptors

The individual parts that come together to form a functional receptor.

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Inhibitory neurotransmitter

A neurotransmitter that decreases the likelihood of a neuron firing by hyperpolarizing the postsynaptic membrane.

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Metabotropic receptors

G protein-coupled receptors that do not have an ion pore and involve a dual mechanism of action.

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G proteins

Molecular switches composed of three subunits (α, β, γ) that regulate signaling pathways via nucleotide binding.

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Active G protein

G protein that is bound to GTP, allowing it to interact with effectors and transmit signals.

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Inactive G protein

G protein that is bound to GDP, preventing it from activating other proteins or effects.

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Hydrolysis of GTP

The reaction that converts GTP to GDP, leading to G protein inactivation.

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Gs and Gi G proteins

Gs stimulates adenylyl cyclase while Gi inhibits it; both are key in cellular signaling.

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Subtypes of G proteins

Different forms of G proteins (e.g., α, β, γ) that vary in effector recognition and function.

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Cyclic AMP (cAMP)

A common second messenger that is involved in signaling pathways.

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Calcium regulation

Control of calcium ion levels inside cells for various functions.

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Calmodulin

A protein that binds calcium and regulates several proteins in response to Ca2+.

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Phosphorylation by kinases

The process where kinases add phosphate groups to proteins, altering their function.

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Study Notes

Synaptic Structure and Function

  • Neurotransmitters are involved in neural communication.
  • Neurotransmitter synthesis, release, and inactivation are crucial processes.
  • Neurotransmitter receptor superfamilies include tyrosine kinase receptors, ionotropic receptors, and metabotropic receptors.

Synapse

  • Synapses are junctions between neurons.
  • Axon terminals (presynaptic elements) release neurotransmitters.
  • Synaptic vesicles store neurotransmitters.
  • Mitochondria provide energy for synaptic function.
  • Postsynaptic densities contain receptors.
  • Synaptic clefts separate pre- and postsynaptic membranes.
  • Pre-synaptic inhibition/facilitation affects signal transmission.
  • Astrocytes play a regulatory role in the synapse.

Neurotransmitters: Traditional Criteria

  • A suspected neurotransmitter must be stored in the presynaptic terminal.
  • Application of the suspected substance should mimic the effects of stimulating the presynaptic terminal at the synapse.
  • The substance should bind to receptors on the postsynaptic cell.
  • Application of an antagonist drug blocking receptors should inhibit the substance's action.
  • A mechanism for neurotransmitter synthesis must exist.
  • A mechanism for inactivation (e.g., enzymatic breakdown, reuptake) must also exist.

Neurotransmitters: Important Notes

  • Receptors determine a neurotransmitter's effect.
  • Neuromodulators alter neurotransmitter function.
  • One axon can release multiple neurotransmitters (coexistence/colocalization).
  • Vertebrates and invertebrates share many neurotransmitters.

Neurotransmitter Types

  • The table lists substances found to possess neurotransmitter or neuromodulatory properties.
  • These include phenethylamines, neuropeptides, amino acids, and cholinergic substances.

Neurotransmitter Synthesis

  • Amino acid neurotransmitters contain an amine group and a carboxyl group.
  • Monoamines contain a single amine group.
  • Acetylcholine is a quaternary amine.
  • Small, water-soluble molecules are ionized.
  • Synthesis occurs from dietary precursors in cell bodies or nerve terminals.
  • Neurotransmitters are packaged into vesicles for release.
  • Neuropeptides are larger and synthesized in cell bodies.
  • They are transported to nerve terminals for release.

Neurotransmitter Release - Exocytosis

  • Neurotransmitter release is a process called exocytosis.
  • Neurotransmitters are stored in synaptic vesicles.
  • Calcium influx triggers vesicle fusion and neurotransmitter release.
  • Neurotransmitter molecules diffuse across the synaptic cleft.

Docking: SNARE Proteins

  • SNARE proteins facilitate vesicle docking and fusion.
  • Calcium entry through channels triggers fusion pore widening.
  • Neurotransmitter molecules then leave the terminal button.

Botulinum Toxin

  • Botulinum toxin blocks acetylcholine release.
  • This blockage prevents muscle contractions and can induce paralysis.

Release of Neurotransmitters: Rate-Controlling Factors

  • Rate of cell firing frequency affects neurotransmitter release.
  • Precursor and enzyme transport affects neurotransmitter replenishment.

Release of Neurotransmitters: Rate-Controlling Factors

  • Rate of cellular firing
  • Transport of precursors and enzymes
  • Presence of heteroreceptors (affecting different NTs)
  • Presence of autoreceptors (responding to the released NT)

Receptor Superfamilies

  • Tyrosine kinase receptors are involved in neuronal development.
  • Ionotropic receptors are ligand-gated ion channels.
  • Metabotropic receptors are G protein-coupled receptors.

Tyrosine Kinase Receptors

  • Activated by neurotrophic factors for maintenance, growth, and development of synapses.
  • They control neuronal growth and survival.
  • Factors like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 and 4 are involved.
  • Phosphorylation alters the protein's structure.

Ionotropic Receptors

  • Channel-linked receptors with pore regions for ions.
  • Fast, rapidly desensitizing responses to neurotransmitters.
  • Subunit heterogeneity, resulting in diverse functional properties.
  • Result in rapid changes in ion flux(eg. Na+, Cl−).

Nicotinic ACh Receptor

  • Ionotropic receptor for acetylcholine (ACh).
  • Function as ligand-gated Na+ channels.
  • Excitatory response.
  • 5 subunits.

Metabotropic Receptors

  • G protein-coupled receptors composed of 7 transmembrane domains.
  • They lack pore regions for direct ion flow.
  • They result in a slower response.
  • They signal indirectly through second messengers.

G Proteins: Structure

  • G proteins are heterotrimeric, with α, β, and γ subunits.
  • Subunit heterogeneity leads to functional diversity.
  • Binding of GTP activates the G protein.
  • Binding of GDP inactivates it.

Mechanism of Action of G Proteins

  • Agonist binding activates the G protein.
  • GTP replaces GDP on the α subunit.
  • The α subunit dissociates from the βγ complex and interacts with effector proteins.
  • Effector proteins, such as enzymes or ion channels, are modified.

Best Characterized G Proteins

  • Table 6.2 identifies G protein targets and their effects.
  • Cholera toxin and pertussis toxin affect G protein activity.
  • This can be used to study G protein function.

Direct Interaction Between G Proteins and Ion Channels

  • G proteins can directly interact with ion channels.
  • This alters ion permeability and results in cellular effects.

Metabotropic Transmission

  • Neurotransmitters bind to receptors
  • G protein activation leads to intracellular signaling.
  • Second messengers relay signals intracellularly.
  • Proteins can be phosphorylated for response.
  • The process results in cellular effects (e.g., changes in ion channels).
  • It's a multifaceted process.

Calcium and Calmodulin

  • Intracellular calcium levels regulate many protein functions.
  • Calmodulin is a calcium-binding protein that modulates downstream events.

Cyclic Nucleotides: cAMP and cGMP

  • cAMP and cGMP are intracellular signaling molecules.
  • They mediate responses regulated by extracellular signals.
  • The process involves various chemical and biological events.

Gene Regulation by Neurotransmitters

  • Neurotransmitters affect gene expression in the brain.
  • Second messengers and transcription factors are involved.
  • cAMP-activated protein kinase (PKA) phosphorylates CREB proteins.
  • CREB then binds to DNA for gene expression modulation.

Immediate Early Genes

  • The immediate early genes (IEGs) are expressed rapidly in response to neuronal activation.
  • They regulate gene expression over longer periods.
  • They are significant in neural plasticity and memory.

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Description

This quiz explores neurotransmission mechanisms, including the roles of transporter proteins, acetylcholinesterase inhibitors, astrocyte function, and selective serotonin reuptake inhibitors (SSRIs). It also covers the mechanisms by which psychoactive drugs affect neurotransmission, the function of protein kinases, the importance of neurotrophic factors, and the characteristics of ionotropic receptors.

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