chapter 22 - Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons Flashcards
Q: What is the most dramatic example of regulation of electrical properties in cell membranes?
action potential
Q: What allows cell membranes to regulate ion flow?
A: Their ability to control the passage of ions between the interior and exterior of the cell.
Q: What are the two main divisions of the vertebrate nervous system?
A:
Central Nervous System (CNS): Brain and spinal cord.
Peripheral Nervous System (PNS): Sensory and motor components.
Q: What are the two main types of cells in the nervous system?
A:
Neurons: Send and receive electrical impulses.
Glial cells: Support various functions and are the most abundant in the CNS.
Q: What are the 3 types of neurons?
A:
Sensory neurons
Motor neurons
Interneurons
Q: What are the types of glial cells and their functions?-
A:
- Microglia: Fight infections and remove debris.
- Oligodendrocytes and Schwann cells: Form myelin sheaths around CNS and peripheral nerves.
- Astrocytes: Regulate access of blood-borne components into the extracellular fluid, forming the blood-brain barrier.
Q: What are the structural components of a neuron?
A:
- Cell body: Contains the nucleus and endomembrane components.
Processes:
- Dendrites: Receive signals.
- Axons: Conduct signals.
Q: What is axoplasm?
A: The cytosol within an axon.
Q: What is a nerve?
A: A tissue composed of bundles of axons.
Q: What is the role of the myelin sheath?
A: Insulates axons, separating segments with nodes of Ranvier.
Q: What distinguishes motor neurons?
A:
- Multiple branched dendrites.
- A single, long axon.
- Terminal structures called synaptic boutons (or terminal bulbs).
Q: What is the function of synaptic boutons?
A: Transmit signals to neurons, muscles, or gland cells.
Q: What is a synapse?
A: The junction between a nerve cell, gland, or muscle cell.
Q: Where do synapses typically occur?
A:
Between axons and dendrites.
Between two dendrites.
Q: What is membrane potential (Vm)?
A: A fundamental property where cells at rest have excess negative charge inside and positive charge outside.
Q: What is resting membrane potential?
A: The electrical potential resulting from the charge distribution.
Q: What are the principles of ion transport?
A:
1. Diffusion: Solutes move from high to low concentration.
Example: Potassium ions diffuse out due to the potassium ion gradient.
- Electroneutrality: Ions in solution are paired with oppositely charged ions.
Example:
Inside the cell: K+ pairs with trapped anions.
Outside the cell: Na+ pairs with Cl-.
What is electrical potential (voltage)?
A:
- Local separation of charges where one region has more positive charges, and another has more negative charges.
- It requires work to create this separation.
Q: Must a solution maintain electroneutrality?
A: Yes, but charges can be separated locally to create electrical potential.
Q: What is current in the context of ion transport?
A:
- The movement of ions (positive or negative).
- Measured in amperes (A).
Q: Why are squid giant axons significant for research? (year)
A:
- Their large size allows for easy insertion of microelectrodes.
- Used since the 1930s to study nerve transmission and measure/control electrical potentials.
Q: What is the resting membrane potential of the squid giant axon?
A: About –60 mV.
Q: Which cells exhibit electrical excitability?
A: Nerve, muscle, and certain other cell types.
Q: What is an action potential?
A:
A rapid change in membrane potential in electrically excitable cells triggered by certain stimuli.
The membrane potential changes from negative to positive and back to negative in a short time.
Q: What does the resting membrane potential depend on?
A:
- Ion concentrations:
Extracellular fluid: Mostly sodium chloride (NaCl).
Cytosol: Contains trapped macromolecules like
proteins and RNA.
- Selective membrane permeability: Specific ion channels help maintain resting potential.
Q: What are leak channels?
A:
Ion channels that form pores through the lipid bilayer.
Characteristics:
Always open (not gated).
Allow potassium and sodium to diffuse
based on ion concentration and
membrane voltage.
Q: Why is the resting potential negative?
A:
Potassium leak channels allow K+ to diffuse out of the cell.
This leaves behind anions without counterions, creating a negative charge inside the cell.
Q: What is the role of the Na+/K+ pump?
A:
Compensates for ion leakage by pumping Na+ out and K+ into the cell.
Key features:
- ATP-dependent process.
- Pumps 3 Na+ ions out for every 2 K+ ions in.
- Maintains the large potassium ion gradient across the membrane.
Q: What is the relationship between ion leak and the Na+/K+ pump?
A: The pump continuously works to restore ionic gradients that are disrupted by ion leakage.
Q: Why do potassium ions leave the cell through leak channels?
A: Due to the concentration gradient of potassium being higher inside the cell than outside.
Q: How does the composition of ions differ between the cytosol and extracellular fluid?
A:
Cytosol: High in K+ with macromolecules like proteins and RNA.
Extracellular fluid: High in Na+ and Cl-.
Q: What is the Nernst equation used for?
A: It describes the relationship between membrane potential and ion concentration, specifically at equilibrium.
Q: What is electrical equilibrium?
A: The state where a chemical gradient is balanced by electrical potential, resulting in an equilibrium (or reversal) potential.
Q: What does the Nernst equation assume when simplified?
A:
- A temperature of 293K.
- A monovalent ion with a valence of 1.
Q: How does the Nernst equation relate membrane potential to ion gradients?
A: For every tenfold increase in the cation gradient, the membrane potential changes by approximately -58 mV.
Q: Why is the simplified Nernst equation incomplete?
A: It does not account for anions or the unequal distribution of multiple ions like Na+, K+, and Cl-.
Q: How do individual ions affect membrane potential?
A:
- K+: Diffuses out of the cell, making the membrane potential more negative
.
- Na+: Flows into the cell, driving the potential in the positive direction (depolarization).
- Cl-: Diffuses into the cell but is repelled by the negative membrane potential unless accompanied by positive ions.
Q: What happens when membrane permeability to Cl- increases?
A:
- Hyperpolarization: Net entry of Cl- without a matching cation makes the membrane potential more negative.
- Cl- enters with Na+ during increased sodium permeability, further decreasing excitability.
Q: What does the Goldman equation describe?
A: The combined effects of multiple ions (Na+, K+, Cl-) on membrane potential, accounting for their relative permeabilities.
Q: How is the Goldman equation different from the Nernst equation?
A: It includes terms for the permeability of each ion, while the Nernst equation deals with only one ion at a time.
Q: What are steady-state ion movements across the plasma membrane?
A:
- K+ only permeability: Membrane potential equals K+ equilibrium potential.
- Slight Na+ permeability: Causes partial depolarization as Na+ leaks in.
- Result: K+ diffuses outward, balancing the inward Na+ movement.
Q: What are the contributions of Goldman, Lloyd, and Katz?
A: They described how gradients of multiple ions contribute to membrane potential and developed the Goldman equation.
Q: How does the Goldman equation estimate resting membrane potential in a squid axon?
A:
Uses relative permeabilities:
- K+: 1.0
- Na+: 0.04 (4%)
- Cl-: 0.45 (45%)
- The estimated potential is -60.3 mV, aligning with the typical measured value of -60 mV.
Q: How does the Goldman equation simplify to the Nernst equation?
A: When the relative permeability of one ion is very high, the Goldman equation reduces to the Nernst equation for that ion.
Q: When can Cl- effects be ignored in the Goldman equation?
A: When the permeability of Na+ (Pna) is much greater than that of K+ (Pk).
Q: What is required for an electrically excitable cell to generate an action potential?
A:
Resting potential: Established by ion gradients and permeability.
Depolarization: Stimulus causing a rapid response.
Voltage-gated channels: Present in addition to leak channels and Na+/K+ pumps.
Q: What is patch clamping?
A:
A method to record ion currents passing through single channels.
Developed by Erwin Neher and Bert Sakmann.
Used in neurobiology to study ion channel function.
Q: How are frog oocytes used in ion channel research?
A:
Channel proteins are synthesized in large amounts.
Studied in lipid bilayers or frog eggs.
Mutations or modifications help determine specific channel regions’ roles.
Q: What is optogenetics?
A: A technique using genetically engineered, light-sensitive channel proteins to manipulate neuronal ion concentrations.
Q: What are the tools used in optogenetics, and their functions?
A:
Bacteriorhodopsin: Inhibits neurons.
Channelrhodopsins: Activates neurons.
Q: How is optogenetics applied?
A: Channel proteins are expressed in neuronal cell cultures or transgenic animals, and responses are observed under a microscope.
Q: How do voltage-gated ion channels respond to changes in voltage?
A: They open or close based on voltage changes across the membrane.
Q: What are ligand-gated ion channels?
A: Channels that open when a specific molecule binds to them.
Q: Which voltage-gated ion channels are responsible for action potential?
A: Voltage-gated Na+ and K+ channels.
Q: What are the structural categories of voltage-gated ion channels?
A:
1. Potassium Channels: Multimeric proteins with four subunits.
2. Sodium Channels: Large monomeric proteins with four domains.
Q: What is common in the structure of both sodium and potassium voltage-gated channels?
A:
Each domain or subunit contains six transmembrane α-helices.
Q: What determines the specificity of ion channels?
A:
1. Size of the central pore.
2. Interaction between ions and oxygen atoms in the amino acids of the selectivity filter.
Q: How do oxygen atoms in the selectivity filter contribute to specificity?
A: They are positioned to interact with ions as they pass through, ensuring the correct ions are selected.
Channel Gating and Inactivation
Q: What is channel gating in voltage-gated sodium channels?
A: The process where channels open rapidly in response to a stimulus and then close again.
Q: Is channel gating all-or-none or partial?
A: All-or-none; channels are either fully open or fully closed.
Q: What acts as a voltage sensor in voltage-gated sodium channels?
A: The fourth transmembrane helix, S4.
Q: What is channel inactivation?
A: A state where the channel cannot reopen immediately, even if stimulated, due to an inactivating particle blocking the channel opening.
Q: What is an action potential?
A: A rapid, large depolarization and repolarization of the neuronal plasma membrane caused by:
Inward movement of Na+.
Outward movement of K+.
Q: How does an action potential propagate?
it travels along the cell membrane, moving away from its point of origin. This movement occurs through a process known as propagation.
Phases of Action Potential
Q: What happens during the depolarizing phase?
A:
Membrane potential rises rapidly after crossing the threshold potential.
Significant Na+ channels activate, causing the potential to peak at approximately +40 mV.
Q: What happens during the repolarizing phase?
A:
Sodium channels inactivate, and voltage-gated K+ channels open.
The membrane repolarizes as K+ exits the cell.
Q: What is the hyperpolarizing phase (undershoot)?
A:
Temporary drop of the membrane potential below the resting level due to increased K+ permeability.
As K+ channels close, the membrane potential returns to the resting level.
Q: What is the absolute refractory period?
A: A phase immediately after an action potential when:
Na+ channels are inactivated.
No action potential can be triggered, regardless of the stimulus.
Q: What is the relative refractory period?
A: A phase during the undershoot when:
Na+ channels recover, but K+ channels are still open.
Membrane potential is below the threshold, requiring a stronger stimulus to trigger another action potential.
Q: What is the Hodgkin Cycle?
A: A positive feedback loop where:
Depolarization opens Na+ channels.
Increased Na+ flow causes further depolarization, opening more channels.
Q: What is subthreshold depolarization?
A:
A small membrane depolarization that does not reach the threshold potential.
No action potential occurs as the membrane potential recovers through K+ leak channels.
Q: How much do ion concentrations change during an action potential?
A: Cellular concentrations of Na+ and K+ hardly change because the ions involved are a small fraction of the total ions in the cell.
Q: What happens during intense neuronal activity?
A: Significant changes in ion concentration can occur with sustained activity.
Q: How is a signal propagated along the axon?
A:
Depolarization spreads passively but decreases in magnitude.
Active regeneration of the action potential ensures it does not lose strength as it travels.
Q: What are the steps of action potential propagation in a nonmyelinated nerve cell?
A:
- Depolarization: Stimulation causes Na+ to rush into the cell, reversing polarity locally.
- Spread: Depolarization spreads to adjacent regions, reaching the threshold.
- Repolarization Initiation: Original region becomes permeable to K+, which exits to restore resting potential
. - Resetting: The membrane at the original site returns to its resting state.
- Continuation: Depolarization triggers the same sequence in the next region, actively propagating the action potential.
Q: What is the function of the myelin sheath?
A:
Acts as an electrical insulator, reducing membrane capacitance.
Allows nerve impulses to spread farther
Q: What is saltatory propagation?
A: A process where action potentials “jump” between nodes of Ranvier, making conduction more rapid than in nonmyelinated axons.
Q: Where are action potentials renewed in myelinated axons?
A: At the nodes of Ranvier, which are spaced close enough to ensure propagation continuity.
Q: What is found at the nodes of Ranvier?
A:
Voltage-sensitive Na+ channels concentrated in the node.
Adhesive proteins between axonal and glial membranes in paranodal regions.
K+ channels in juxtaparanodal regions.
Q: What are synapses?
: Points of contact where signals are transmitted between neurons or to other cell types.
Q: How do electrical synapses work?
A: The presynaptic and postsynaptic neurons are connected by gap junctions, allowing ions to pass directly without delay.
Q: What is a chemical synapse?
A: A type of synapse where presynaptic and postsynaptic neurons are separated by a synaptic cleft, and the signal is transmitted chemically.
Q: How are neurotransmitters released and transmitted?
A:
1. Stored in synaptic boutons of the presynaptic neuron.
- Released when an action potential reaches the bouton.
- Diffuse across the synaptic cleft to bind receptors on the postsynaptic membrane.
- Converted into an electrical signal to excite or inhibit the postsynaptic cell.
Q: What are the two classes of neurotransmitter receptors?
A:
Ionotropic receptors: Ligand-gated ion channels.
Metabotropic receptors: Indirectly affect the cell via messenger systems.
Q: What effects do neurotransmitters have on the postsynaptic neuron?
A:
Excitatory: Cause depolarization (e.g., acetylcholine, glutamate, serotonin).
Inhibitory: Cause hyperpolarization (e.g., GABA, glycine).
Criteria for Neurotransmitters
Q: What are the criteria for a molecule to qualify as a neurotransmitter?
A:
Natural presence in the presynaptic neuron.
Released when the neuron is stimulated.
Appropriate response elicited in the synaptic cleft.
Common Neurotransmitters
Acetylcholine:
Most common in vertebrate neuromuscular junctions.
Excitatory.
Used in cholinergic synapses.
Catecholamines (dopamine, norepinephrine, epinephrine):
Tyrosine derivatives.
Synthesized in the adrenal gland.
Used in adrenergic synapses.
Amino Acids and Derivatives:
Excitatory: Glutamate, serotonin.
Inhibitory: GABA, glycine.
Neuropeptides:
Act on groups of neurons with long-lasting effects.
Example: Enkephalins inhibit pain perception.
Endocannabinoids:
Lipid derivatives that inhibit presynaptic neurons.
THC from cannabis stimulates these receptors
Q: How does calcium regulate neurotransmitter secretion?
A:
Action potential depolarizes the bouton.
Voltage-gated calcium channels open, increasing Ca²⁺ concentration.
Neurotransmitters stored in neurosecretory vesicles are released.
Calcium and Vesicle Dynamics
Q: How does calcium influence vesicle release in the synaptic bouton?
A:
Mobilizes vesicles held in storage for rapid release.
Causes docked vesicles to fuse with the plasma membrane, releasing neurotransmitters via exocytosis.
Q: What proteins mediate docking and fusion of vesicles with the plasma membrane?
A:
t-SNAREs and v-SNAREs facilitate vesicle fusion.
Synaptotagmin binds calcium, undergoes a conformational change, and promotes efficient SNARE interactions.
Q: What is the “active zone” in the synaptic bouton?
A:
The site where vesicles dock and fuse, located near calcium channels for efficient neurotransmitter release.
Q: What is kiss-and-run exocytosis?
A: A transient release method where a vesicle briefly fuses with the plasma membrane, releases neurotransmitter, and reseals.
Q: How are neurotransmitters detected by postsynaptic neurons?
A: Each neurotransmitter binds to specific receptors on the postsynaptic cell membrane, triggering excitatory or inhibitory effects.
Q: What type of receptor is nAchR, and what happens when it binds acetylcholine?
A:
It is a ligand-gated Na⁺ channel.
Binding of two acetylcholine molecules opens the receptor, allowing Na⁺ to enter and depolarize the cell.
Q: What neurotoxins affect nAchR?
A:
α-bungarotoxin and cobratoxin covalently bind to nAchRs.
Curare (contains d-tubocurarine) and some snake venoms compete with acetylcholine, preventing depolarization.
Q: What are antagonists and agonists in cholinergic systems?
A:
Antagonists: Block acetylcholine binding, preventing depolarization.
Agonists: Mimic acetylcholine, causing depolarization, but are not rapidly inactivated.
Q: How does the GABA receptor function, and what is its effect?
A:
It is a ligand-gated Cl⁻ channel.
When open, it allows Cl⁻ to enter the cell, causing hyperpolarization and reducing action potential likelihood.
Q: How do benzodiazepines interact with GABA receptors?
A: They enhance GABA’s effects, promoting increased hyperpolarization.
NMDA Receptor
Q: What is the NMDA receptor, and why is it significant?
A:
It is an ionotropic receptor for glutamate, permeable to Na⁺ and Ca²⁺ when glutamate binds.
Plays a critical role in memory and neuronal plasticity.
Q: What is a common use for NMDA receptor antagonists?
A: They are frequently used as anesthetics.
Q: Why must neurotransmitters be inactivated after release?
A: To prevent prolonged stimulation or inhibition of the postsynaptic neuron.
Q: What are the two primary mechanisms of neurotransmitter inactivation?
A:
Degradation (e.g., enzymatic breakdown).
Reuptake into the presynaptic cell or nearby support cells.
Q: How does acetylcholinesterase function?
A:
Hydrolyzes acetylcholine into acetic acid and choline.
Inhibited by compounds like carbamoyl esters, nerve gases (e.g., sarin), and certain insecticides.
Q: What is the role of neurotransmitter reuptake?
A:
Pumps neurotransmitters back into the presynaptic neuron or nearby support cells within milliseconds.
Antidepressants like Prozac block reuptake to prolong neurotransmitter action.
Q: What are PSPs, and how do they work?
A:
Postsynaptic potentials are incremental changes in membrane potential caused by neurotransmitter binding.
PSPs can be excitatory (EPSP) or inhibitory (IPSP) depending on the neurotransmitter.
S
Q: What is temporal summation?
A:
Occurs when rapid successive action potentials sum up EPSPs over time, pushing the postsynaptic cell past its threshold.
Q: What is spatial summation?
A:
Occurs when multiple action potentials from different synapses release neurotransmitters simultaneously, increasing the likelihood of reaching the action potential threshold.
Sensory neurons:
Detect stimuli.
.
Motor neurons:
Transmit signals from the CNS to muscles and glands.
Interneurons:
Process signals and transmit information within the nervous system
