Chapter 11.3 Channels and the Electrical Properties of Membranes Flashcards
__ are channels that connect the cytoplasm of adjacent animal cells, while __ perform a similar function in plant cells.
- Gap junctions
- plasmodesmata
Large, permissive channels found in the outer membranes of bacteria, mitochondria, and chloroplasts, allowing the passage of small molecules.
porins
Why would large channels that connect the inside of a cell to the extracellular space be dangerous?
They could disrupt the cell’s internal environment, as some bacterial toxins form such large channels to kill cells.
- Have narrow, highly selective pores that open and close rapidly to control the transport of specific inorganic ions like Na⁺, K⁺, Ca²⁺, and Cl⁻.
- allow specific inorganic ions to diffuse rapidly down their electrochemical gradients, facilitating passive transport across the lipid bilayer.
Ion channels
How fast can ions pass through an open ion channel?
Up to 100 million ions can pass through an open ion channel per second, which is 100,000 times faster than the fastest transporter.
Can ion channels be coupled to an energy source for active transport?
No, ion channels mediate passive transport only, allowing ions to flow down their electrochemical gradients.
What percentage of a cell’s weight is typically water?
About 70%
Produced by the difference in concentration of all solutes on either side of a semi-permeable membrane.
osmotic gradient
How do cells balance the osmotic gradient caused by intracellular solutes?
the concentration of inorganic ions, like Na⁺ and Cl⁻, in the extracellular fluid.
- a combination of active transport, passive diffusion, the use of compatible solutes, and specialized channels,
How long does it take for cell volume to equilibrate in response to osmotic changes?
in minutes or less due to the permeability of biological membranes to water.
Why does osmosis play only a minor role in regulating cell volume in most animal cells?
Most of the cytoplasm in animal cells is in a gel-like state, which resists large changes in volume due to changes in osmolarity.
Are water channels in the plasma membrane that facilitate rapid water movement across the membrane.
Aquaporins
Where are aquaporins particularly abundant, and why?
Cells that transport large volumes of water, such as kidney epithelial cells and exocrine gland cells.
Water flow is regulated by hormones like __, which control the concentration of aquaporins in the plasma membrane.
antidiuretic hormone (vasopressin),
ADH (vasopressin) increases water reabsorption in the kidneys by promoting the insertion of __ into the plasma membranes of kidney tubule cells. This __ urine volume and helps __ the urine, especially when the body is dehydrated or blood osmolarity is high.
- aquaporins
- reduces
- concentrate
Cells lining the ducts of exocrine glands secrete large volumes of fluid through a coordinated process. (1)__, such as Na⁺/K⁺ ATPase, actively transport Na⁺ (2)__ of the cell and Cl⁻ into the (3)__, creating a high concentration of these ions in the lumen. This accumulation generates an osmotic gradient that draws water into the lumen to balance the solute concentration. Water rapidly follows through (4)__, specialized water channels located in the plasma membrane of the ductal cells. The combined movement of ions and water results in the secretion of large volumes of fluid into the (5)__, which is essential for the proper functioning of exocrine glands, including the secretion of saliva, sweat, and digestive enzymes.
1) Ion pumps
2) out
3) ductal lumen
4) aquaporins
5) ducts
Aquaporins form __, with each monomer containing an __.
- tetramers
- aqueous pore
How many water molecules can each individual aquaporin channel pass per second?
about 1 billion
The feature of aquaporin pore that aids in water transport is that the pore is lined with (1)__ that provide (2)__, helping to align and orient water molecules in a single row.
1) hydrophilic amino acids
2) transient (impermanent) hydrogen bonds
In aquaporins, the (1)__ lining the hydrophilic face of the pore align water molecules, and strategically placed (2)__ a central water molecule, preventing (3)__ from passing through. (3)__ diffuses extremely rapidly by being relayed from one water molecule to the next.
1) carbonyl groups (C=O)
2) asparagines tether
3) H⁺
The arrangement of water molecules in the aquaporin pore affect hydrogen bonding because the arrangement (1)__ the entire column of water molecules, allowing each water molecule to act as a (2)__ for its inner neighbor.
1) bipolarizes
2) hydrogen-bond acceptor
What is the primary challenge that aquaporins face compared to ion channels?
Aquaporins must allow the rapid passage of water while completely blocking the passage of ions to maintain ion gradients across membranes.
How does the three-dimensional structure of aquaporins contribute to their selectivity for water?
Aquaporins have a narrow pore that allows water molecules to pass in single file, guided by carbonyl oxygens lining one side of the pore.
Why are aquaporins impermeable to hydrated ions such as K⁺, Na⁺, Ca²⁺, or Cl⁻?
The pore is too narrow for hydrated ions to enter, and dehydrating an ion would incur a high energy cost that cannot be compensated by interactions with the hydrophobic wall of the pore.
Aquaporins cannot conduct H⁺ because H⁺ is mainly present as (1)__, which diffuses rapidly through water using a relay mechanism that relies on the making and breaking of hydrogen bonds, which aquaporins block.
1) H₃O⁺ (hydronium)
What role do strategically placed asparagines play in aquaporins?
They bind to the oxygen atom of the central water molecule in the pore, creating a bipolarity that prevents the participation of this water molecule in an H⁺ relay.
A channel that exhibits ion selectivity, allowing certain inorganic ions to pass while excluding others.
Ion channel
The narrowest part of the ion channel that forces permeating ions into close contact with the channel walls, determining which ions can pass based on size and charge.
selectivity filter
When passing through ion channels, ions interact with water molecules in different ways. Some ions (1)__ most or all of their associated water molecules to pass through the channel, effectively becoming “(2)__.” In contrast, other ions can pass through as (3)__ or (3)__ ions, retaining some of their water molecules. This interaction influences the permeability and selectivity of the ion channels, as the degree of hydration can affect the ion’s ability to traverse the channel.
1) shed
2) dehydrated
3) hydrated or partially hydrated
How do ion channels differ from aqueous pores in terms of their state?
Ion channels are gated, meaning they are not continually open and can open or close in response to specific stimuli (e.g., voltage changes, mechanical stress, or ligand binding). In contrast, aquaporins are generally constitutively open aqueous pores that facilitate the rapid movement of water based on osmotic gradients. While aquaporins can be influenced by factors like hormonal signaling, they do not undergo the same gating mechanisms as ion channels, allowing water to flow continuously when present in the membrane.
With prolonged stimulation, ion channels may enter a __ “__” or “__” state, becoming refractory to further opening until the stimulus is removed. This state prevents the channels from responding to additional signals, allowing the cell to reset before it can respond to new stimuli.
- closed; desensitized; inactivated
What are the main types of stimuli that cause ion channels to open? (3)
1) Change in voltage across the membrane (voltage-gated channels)
2) Mechanical stress (mechanically gated channels)
3) Binding of a ligand (ligand-gated channels)
What are the two types of ligands that can regulate ligand-gated ion channels? (2)
1) Extracellular mediators, such as neurotransmitters (transmitter-gated channels)
2) Intracellular mediators, such as anions or nucleotides (ion-gated and nucleotide-gated channels)
__, the addition of a phosphate group, can enhance or inhibit channel opening, while __, the removal of a phosphate group, can reverse these effects. This regulatory mechanism influences whether the ion channel is open or closed, impacting ion flow across the membrane and ultimately affecting cellular signaling and function.
- Phosphorylation
- dephosphorylation
How many types of ion channels have been identified, and are new types still being discovered?
More than 200
Ion channels are characterized by the __ they conduct, the __ by which they are gated, and their __ and __ in the cell and specific cell types.
- ions
- mechanism
- abundance
- localization
Ion channels are responsible for the electrical excitability of __ and mediate most forms of electrical signaling in the __. (what type of cell in the body?; what system in the body?)
- muscle cells
- nervous system
A single neuron can typically contain __ kinds of ion channels, located in different domains of its plasma membrane.
10 or more
Are ion channels found only in electrically excitable cells?
No, ion channels are present in all animal cells, as well as in plant cells and microorganisms.
Give an example of a plant and a microorganism that utilize ion channels.
The mimosa plant uses ion channels to propagate its leaf-closing response, while the single-celled motile Paramecium uses them to reverse direction after a collision.
- A subset of K⁺ channels that open even in an unstimulated or “resting” cell.
- They make the plasma membrane much more permeable to K⁺ than to other ions, helping to maintain the membrane potential.
K⁺ leak channels
- arises from a difference in electrical charge across a membrane due to a minute excess of positive ions on one side and a minute deficit on the other.
- the difference in electric potential between the interior and the exterior of a biological cell.
- principle: If two solutions of different ion concentrations are separated by a permselective membrane a potential difference between the two solutions is established.
membrane potential
Passive ion movements, particularly through __, make the largest contribution to the electrical potential across the plasma membrane. It primarily contributes to the membrane potential in animal cells.
- K⁺ leak channels
__ balances the charge carried by fixed anions (negatively charged organic molecules) inside the cell and is actively pumped in by the Na⁺-K⁺ pump.
- K⁺
The equilibrium of K⁺ affects membrane potential because K⁺ tends to move out of the cell down its concentration gradient, leaving behind unbalanced negative charges, creating an electrical field that opposes further __.
K⁺ efflux
Defined as the voltage at which the electrical driving force on K⁺ exactly balances the effect of its concentration gradient, resulting in no net flow of ions across the membrane.
Resting membrane potential
Used to quantify the equilibrium condition and calculate the theoretical resting membrane potential based on internal and external ion concentrations.
Nernst equation
Why is the actual resting membrane potential often not equal to the value predicted by the Nernst equation for K⁺?
The plasma membrane of a real cell is not exclusively permeable to K⁺; therefore, other ions also influence the actual resting membrane potential.
The flow of inorganic ions is driven by the __ for that ion, which combines the effects of the voltage gradient and the concentration gradient.
electrochemical gradient
- When the voltage gradient and concentration gradient for an ion balance each other, the electrochemical gradient for the ion is zero, resulting in no net flow of the ion through the channel. What do you call this?
- refers to the specific membrane potential at which the concentration gradient for a particular ion is balanced by the electrical gradient, resulting in no net movement of that ion across the membrane.
Equilibrium potential or Nernst potential
How is the equilibrium potential for an ion calculated?
Nernst equation
the primary contributor to the resting potential of a cell
K⁺ equilibrium mechanism
When the Na⁺-K⁺ pump is suddenly inactivated, there is an immediate slight __ in the membrane potential due to the pump’s electrogenic nature, as it normally contributes to the maintenance of the resting membrane potential by moving more Na⁺ out of the cell than K⁺ in. However, the major resting potential can persist for several minutes due to the presence of other ion channels and the overall ionic balance in the cell. Over time, without the pump’s activity, the resting potential will eventually decline further.
drop
After stopping the Na⁺-K⁺ pump, the ion gradients established by the pump will gradually __. This allows __ to enter the cell, leading to a new resting state where the concentrations of Na⁺, K⁺, and Cl⁻ reach equilibrium. As a result, the membrane potential __, ultimately leading to a lower resting potential than what was maintained during active pumping.
- diminish
- Na⁺
- decreases
What is the typical range of resting potential in animal cells?
-20 mV and -120 mV
What was the first ion channel to be crystallized and studied by x-ray diffraction?
bacterial K⁺ channel
K⁺ channels conduct K⁺ ions much faster than Na⁺ despite similar sizes due to specific structural features, including the arrangement of __ in the __.
- carbonyl oxygens
- selectivity filter
What is the effect of a single amino acid substitution in the pore of a K⁺ channel?
loss of ion selectivity and result in cell death
The bacterial K⁺ channel consists of __ identical transmembrane subunits that form a __ through the membrane, with each subunit contributing two transmembrane __.
- four
- central pore
- α-helices
In the bacterial K⁺ channels, this part from the four subunits forms a narrow pore lined with carbonyl oxygen atoms, which allows K⁺ ions to enter while excluding Na⁺ ions.
selectivity loops
selectivity filter in K+ channel function:
A K⁺ ion must (1)__ almost all of its bound water molecules to enter the filter, where it interacts with (2)__ that are spaced to accommodate K⁺, while Na⁺ cannot enter due to insufficient proximity of the (2)__.
1) lose
2) carbonyl oxygens
When K⁺ channel structure closes, the inner helices of the K⁺ channel __ to constrict the pore at the cytosolic end, blocking ion entry with bulky hydrophobic side chains.
tilt
Other ion channels also use similar gating principles, where the channel’s pore helices are __ __ to sensor domains that induce conformational changes in response to stimuli, opening or closing the ion-conducting pathway.
- allosterically coupled
- Protein channels that respond to mechanical forces in their environment, allowing cells to sense and react to changes such as pressure, shear forces, and osmotic pressure.
- rare, often embedded in complex structures, and their gating mechanisms require attachment to the extracellular matrix or cytoskeleton, making them challenging to isolate and study.
Mechanosensitive channels
Why is it difficult to study mechanosensitive channels?
Mechanosensitive channels are rare, often embedded in complex structures, and their gating mechanisms require attachment to the extracellular matrix or cytoskeleton, making them challenging to isolate and study.
- It is a mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals.
- essential for touch sensation, detecting bladder fullness, and play a crucial role in developmental processes and blood pressure regulation.
- formed from three identical subunits, each containing 36 transmembrane helices that create a dome-like structure, with a central hub that forms the ion-conducting pore.
Piezo ion channels
Researchers were able to identify Piezo ion channels by using __ __ to find cell lines that opened an ion channel in response to mechanical pressure and systematically disrupted genes encoding proteins with membrane-spanning helices.
definition: a versatile electrophysiological tool for understanding ion channel behavior.
- patch clamping
Piezo channels are formed from __ identical subunits, each containing __ transmembrane helices that create a __-__ structure, with a central hub that forms the __-__ __.
- three
- 36
- dome-like
- ion-conducting pore
Bacteria open __ in hypotonic environments to leak small molecules when osmotic pressure becomes dangerous, allowing them to maintain essential macromolecules while quickly losing smaller ones.
mechanosensitive channels
What are the two types of mechanosensitive channels found in bacteria? (2) What are their pore sizes?
1) MscS channel (small conductance, opening at low to moderate pressures) - 1.3 nm in diameter
2) MscL channel (large conductance, opening at high pressures). - 3 nm in diameter
What is the fundamental task of a neuron?
to receive, integrate, conduct, and transmit signals.
A human neuron can be as long as __, such as a neuron extending from the spinal cord to a muscle in the foot.
1 meter
A neuron consists of a __(containing the nucleus), one long __ (which conducts signals away), and multiple __(which receive signals from other neurons).
- cell body
- axon
- dendrites
provide an enlarged surface area to receive signals from the axons of other neurons, and they can receive as many as 100,000 inputs on a single neuron.
Dendrites
Neuron signals consist of changes in the __ __ across the plasma membrane.
electrical potential
The electrical disturbance as it travels along a neuron __ with increasing distance unless the neuron expends energy to __ the signal.
- weakens
- amplify
Can conduct signals passively, without amplification, over short distances.
Small neurons
Larger neurons use an active signaling mechanism that amplifies the signal as it travels, generating an __ __ (__ __) that propagates rapidly without attenuation.
action potential (nerve impulse)
An action potential is triggered when an electrical stimulus exceeds a certain __ strength, leading to rapid electrical activity.
- threshold
- A channel responsible for the generation and propagation of action potentials in neurons.
- generate action potentials in electrically excitable cells, including neurons, muscle, endocrine, and egg cells.
Voltage-gated cation channel
In nerve and skeletal muscle cells, action potential is triggered by the __ of the plasma membrane, where the membrane potential shifts to a __ __ value inside.
- depolarization
- less negative
When voltage-gated Na+ channels open during depolarization, __ ions enter the cell, further depolarizing the membrane and opening more Na+ channels, creating a __ feedback loop.
- Na+
- positive
What stops the depolarization process in a neuron during an action potential? (2)
(1) Na+ channels automatically inactivate
(2) voltage-gated K+ channels open to restore the membrane potential to a negative value.
The __ __ consists of a single polypeptide chain with four similar domains, each contributing to the central channel and containing a voltage sensor (S4 helix) with positively charged amino acids. During __, the S4 helices experience electrostatic forces that cause them to twist, exposing their charges to the opposite side of the membrane, which opens the channel.
- Na+ channel
- depolarization
__ __ automatically inactivate after opening, even though the membrane remains depolarized, and they cannot reopen until the membrane potential returns to its initial negative value.
Na+ channels
Delayed K+ channels open during the __ __ of the action potential, allowing K+ to __ the cell and __ the membrane.
- falling phase/repolarization
- exit
- repolarize/hyperpolarize
The time needed for Na+ channels to recover from inactivation, limiting the neuron’s repetitive firing rate and ensuring unidirectional action potential propagation.
refractory period
Along neurons membrane, action potential propagates as a __, with the depolarization of one patch of membrane triggering depolarization in neighboring regions, sweeping across the membrane.
wave
The __-__ __ speeds up ion pumping to restore electrochemical gradients during rapid firing, and neurons with high energy consumption preferentially take up radioactive glucose, which is imaged in a Positron Emission Tomography (PET) scan.
- Na+-K+ pump
The (1)__ insulates axons, increasing the speed of action potential conduction by preventing current leakage and allowing the action potential to jump between (2)__ in a process called (3)__.
1) myelin sheath
2) nodes of Ranvier
3) saltatory conduction
__ is a demyelinating disease where the immune system attacks the myelin sheaths in some areas of the central nervous system. This slows or halts the propagation of nerve impulses, often leading to severe neurological damage.
Multiple sclerosis
What cells form the myelin sheath in the peripheral and central nervous systems? (2)
1) Schwann cells form the myelin sheath in the peripheral nervous system.
2) Oligodendrocytes form the myelin sheath in the central nervous system.
1) Schwann cells form the myelin sheath in the __nervous system.
2) Oligodendrocytes form the myelin sheath in the __ nervous system.
1) peripheral
2) central
(1)__ and (2)__ wrap multiple layers of their plasma membrane tightly around the axon, creating a myelin sheath that insulates the axon, preventing current leakage.
1) Schwann cells
2) oligodendrocytes
(1)__ are gaps in the myelin sheath where Na+ channels are concentrated. Action potentials jump from one node to the next in (2)__, speeding up signal transmission and conserving metabolic energy.
1) Nodes of Ranvier
2) saltatory conduction
What are the two main advantages of saltatory conduction? (2)
1) Faster transmission
2) Energy conservation
(1)__, developed in the 1970s and 1980s, allows the study of individual ion channels by recording (2)__ flowing through a small patch of membrane. It has enabled detailed examination of ion channels in various cell types, even in small cells like yeast, which cannot be studied using traditional electrophysiology methods.
1) Patch-clamp recording
2) currents
Patch-clamp recording shows that ion channels, such as voltage-gated Na+ channels, open in an (1)__ fashion. They open (2)__, with a voltage-dependent probability, but when open, they always allow the same amount of ions to pass through.
1) all-or-nothing
2) stochastically/randomly
Conductance of a voltage-gated Na+ channel: when a voltage-gated Na+ channel is open, it allows more than __ ions to pass through per millisecond, maintaining a consistent conductance level.
1000
The __ __ recorded across a membrane reflects the total number of open ion channels at any given time, rather than the degree to which individual channels are open.
aggregate current
The interior of a resting neuron or muscle cell has an electrical potential of about 40-100 mV __ negative than the external environment, creating a strong voltage gradient across the plasma membrane.
more
Changes in __ __ alter the stability of the open, closed, and inactivated conformations of ion channels. These channels can “flip” between conformations when influenced by the strong electrical field across the plasma membrane.
membrane potential
The __ __ across the plasma membrane can reach 100,000 V/cm, which significantly influences the behavior of charged proteins like Na+ channels, affecting their conformation and gating properties.
voltage gradient
Patch-clamp recording is a technique that measures the ionic current passing through individual ion channels in a __ __ of membrane using a micropipette. The membrane potential is maintained at a set value using an __ __, allowing detailed study of ion channel behavior.
- small patch
- electronic clamp
In patch-clamp recording, the __ forms an extremely tight seal with the membrane, ensuring that current can only pass through the ion channels in the membrane covering its tip, allowing precise measurement of ionic flow.
micropipette
Two configurations used in patch-clamp recording:
1) __: The micropipette remains connected to the rest of the cell, allowing the study of ion channels in their natural environment.
2)__: The membrane is isolated, making it easier to manipulate the solution on either side of the membrane to test the effects of different solutes. It can also be used to change the orientation of the membrane, exposing the cytoplasmic surface inside the pipette.
1) Attached Patch
2) Detached Patch
are ion channels that open in response to changes in membrane potential, allowing the flow of cations (such as Na+, K+, or Ca2+). These channels can generate action potentials in various cell types, including neurons, muscle cells, and endocrine cells.
Voltage-gated cation channels
The diversity of voltage-gated cation channels is caused by __ __ and the __ __ of RNA transcripts, resulting in a variety of channel types with different structural and functional properties.
- multiple genes
- alternative splicing
How many voltage-gated K+ channel genes are found in different organisms? (Give two organisms)
1) Saccharomyces cerevisiae (yeast) has 1 gene encoding a voltage-gated K+ channel.
2) Caenorhabditis elegans (worm) has 68 genes encoding different but related K+ channels.
This indicates a large diversity in ion channel genes even in simple organisms.
Mutations in ion channel genes can lead to various diseases, depending on the cells affected. Examples include (2):
1) Myotonia: Delayed muscle relaxation due to faulty Na+ channels in skeletal muscle.
2) Epilepsy: Caused by mutations in Na+ or K+ channels in the brain, leading to excessive synchronized neuronal firing and seizures.
A disease caused by mutations in Na+ or K+ channels in the brain, leading to excessive synchronized neuronal firing and seizures.
Epilepsy
A disease that causes delayed muscle relaxation due to faulty Na+ channels in skeletal muscle.
Myotonia
How do neurons differ in firing action potentials? (1-3)
The combination of (4)__, (5)__, and (6)__ channels expressed in a neuron determines its firing pattern.
1) Some fire up to 300 times per second.
2) Others fire in short bursts separated by silence.
3) Some fire only once at a time.
Threshold for Action Potential Initiation: Varies among neurons, affecting how easily they can fire.
Refractory Periods: Variation in the duration of refractory periods influences firing frequency and responsiveness.
Frequency of Action Potentials: Different firing rates can encode the intensity of stimuli.
4-6) Na+, K+, and Ca2+
In some cells, such as muscle, egg, and endocrine cells, (1)__ generate action potentials instead of Na+ channels, playing a key role in cellular signaling and function.
voltage-gated Ca2+ channels
How many neurons and synaptic connections are estimated to be in the human brain?
approximately 10¹¹ neurons and 10¹⁴ synaptic connections
What allows the brain to remain stable despite changes over time? One theory suggests that neurons are (1)__. They constantly adjust the expression of ion channels and neurotransmitter receptors to maintain stable function, even as neural circuitry is modified by experience, learning, memory, and aging.
1) self-tuning devices
The firing properties of neurons are largely determined by the ion channels they express. The number of __ (Na+ and Ca²⁺) and __ (K⁺) channels can be adjusted to maintain the neuron’s characteristic firing behavior.
- depolarizing
- hyperpolarizing
Neurons can _______________ in their membranes as conditions change. This adjustment helps them maintain stable firing behavior, a process that reflects homeostatic control
modify the number of ion channels
Understanding how neurons self-regulate ion channels to maintain stable firing properties is crucial because it reveals insights into (1)__, (2)__, and (3)__.
1) homeostatic control
2) neural plasticity - (or neuroplasticity) refers to the brain’s ability to change, adapt, and reorganize itself in response to experiences, learning, and environmental factors.
3) potential interventions in neurological disorders
When an action potential reaches the nerve terminal of a presynaptic cell:
1) It stimulates the release of __ from synaptic vesicles.
2) The (1) bind to ___ in the postsynaptic cell membrane.
3) This opens the ion channels, causing ion flow that alters the __ of the postsynaptic cell, transmitting the signal.
1) neurotransmitters
2) transmitter-gated ion channels
3) membrane potential
__ __ contain neurotransmitter molecules and are released when they fuse with the plasma membrane of the nerve terminal, allowing neurotransmitters to enter the synapse and bind to the postsynaptic receptors.
Synaptic vesicles
When an action potential reaches the presynaptic cell, it causes the __ of the membrane, which opens voltage-gated Ca²⁺ channels. The influx of Ca²⁺ triggers the release of __ stored in synaptic vesicles through __.
- depolarization
- neurotransmitters
- exocytosis
Neurotransmitters are removed from the synaptic vesicle are either:
1) __ by specific enzymes in the synaptic cleft.
2) __ by being taken up by the presynaptic cell or surrounding glial cells via Na⁺-dependent neurotransmitter symporters.
1) Destroyed
2) Recycled
__-__ __ __ (__ __) convert chemical signals into electrical signals by opening in response to neurotransmitter binding. They allow ions to flow through the membrane, changing the membrane potential at the postsynaptic site.
- Transmitter-gated ion channels
- ionotropic receptors
Significance of rapid neurotransmitter removal from the synapse:
1) __ of signaling.
2) Decreased chances of influencing __.
3) Clears the cleft before the next neurotransmitter release, ensuring __ of repeated signals.
1) Temporal precision
2) neighboring cells
3) accurate timing
(1)__ respond to neurotransmitters and are relatively insensitive to membrane potential. In contrast, (2)__ respond to changes in membrane potential and are responsible for the self-amplifying excitation of action potentials.
1) Transmitter-gated ion channels
2) voltage-gated ion channels
1) __ open nonselective cation channels (Na⁺, Ca²⁺, and K⁺), causing depolarization of the postsynaptic membrane, moving it closer to the action potential threshold.
2) __ open Cl⁻ channels, making the postsynaptic membrane more negative (hyperpolarization) and suppressing action potential firing.
1) Excitatory neurotransmitters
2) Inhibitory neurotransmitters
__ __ open in response to inhibitory neurotransmitters, allowing Cl⁻ to enter the cell. This buffers the membrane potential by counteracting depolarization, making it harder for excitatory signals to reach the action potential threshold.
Cl⁻ channels
Which neurotransmitters are generally excitatory or inhibitory? Give two examples each.
1) Excitatory: Acetylcholine, Glutamate.
2) Inhibitory: GABA, Glycine.
(Note: Some neurotransmitters, like acetylcholine, can be either excitatory or inhibitory depending on the receptor and location.)
1) Opening K⁺ channels causes __ because K⁺ ions flow out of the cell, moving the membrane potential closer to the equilibrium potential for K⁺, which is typically more negative (around -90 mV in most cells). This makes the inside of the cell more negative relative to the outside, causing hyperpolarization.
2) Opening Cl⁻ channels can __ membrane potential by allowing Cl⁻ ions to flow into the cell (or out, depending on the intracellular Cl⁻ concentration). This generally makes the membrane potential more negative (if Cl⁻ enters) or stabilizes it, preventing excessive __. However, the specific effect depends on the cell’s resting Cl⁻ equilibrium potential, which varies by cell type.
1) hyperpolarization
2) buffer; depolarization
Major class of neurotransmitter receptors: Fast-acting ion channels that respond to neurotransmitters like acetylcholine, glutamate, glycine, and GABA, mediating immediate and brief excitatory or inhibitory signals.
Ionotropic receptors
Major class of neurotransmitter receptors: G-protein-coupled receptors that indirectly regulate ion channels via intracellular signaling, providing slower, more complex, and longer-lasting effects.
Metabotropic receptors
Major class of neurotransmitter receptors (2)
1) Ionotropic receptors
2) Metabotropic receptors
Toxins like __ block the action of inhibitory neurotransmitters (such as glycine) by binding to their receptors, preventing inhibitory action, leading to symptoms like muscle spasms, convulsions, and potentially death.
strychnine
A __ __ is the specialized chemical synapse between a motor neuron and a skeletal muscle cell, where acetylcholine is released from the nerve terminal, triggering muscle contraction.
neuromuscular junction
__ __ are densely packed at the neuromuscular junction, with about 20,000 receptors per square micrometer in the muscle-cell plasma membrane. It opens when two acetylcholine molecules bind to its pentameric complex, inducing a conformational change that allows the channel to flicker open.
Acetylcholine receptors
After acetylcholine binds to the receptor at the neuromuscular junction, the channel flickers between open and closed states with a higher probability of being __. Once acetylcholinesterase hydrolyzes acetylcholine, the concentration __, and the receptor returns to its (3)__ __. The channel typically closes within about 1 millisecond after acetylcholine is hydrolyzed, well before (3)__occurs.
- open
- lowers
- resting state; desensitization
The acetylcholine receptor allows the passage of (1-3)__,__, and __. Clusters of negatively charged amino acids near the pore exclude negative ions and encourage the passage of cations, especially (4)__.
1-3) Na⁺, K⁺, and Ca²⁺
4) Na⁺
At resting potential, the voltage gradient and concentration gradient for Na⁺ both act to drive Na⁺ __ (into/ouside) the cell, causing a large net __ (influx/eflux) of Na⁺ through the acetylcholine receptor and membrane depolarization, which signals __ __ (what mechanism in the body).
- into
- influx
- muscle contraction
__ regulate acetylcholine signaling at the neuromuscular junction. It rapidly hydrolyzes acetylcholine in the synaptic cleft, lowering its concentration and allowing the acetylcholine receptor to return to its resting state within about 1 millisecond.
Acetylcholinesterase
What types of neurotransmitters activate transmitter-gated ion channels similar to acetylcholine receptors? (4)
1) Acetylcholine
2) serotonin
3) GABA
4) glycine
Unlike other transmitter-gated ion channels, __-__ __ __ are constructed from a distinct family of subunits that form tetramers, resembling the structure of K⁺ channels.
glutamate-gated ion channels
How are the many subtypes of transmitter-gated ion channels generated? (2)
1) different subunit combinations, which are produced either by distinct genes
2) alternative RNA splicing from a single gene product.
What factors contribute to the diversity of transmitter-gated ion channels in neurons? (4)
1) ligand affinities
2) channel conductances
3) rates of opening and closing
4) sensitivities to drugs and toxins
It is possible to design drugs that target __ __ of transmitter-gated ion channels, allowing for precise influence over particular __ __ by focusing on neurons expressing different subunit combinations.
- specific subtypes
- brain functions
__ __ target synapses primarily by binding to transmitter-gated ion channels, affecting neurotransmitter actions and altering synaptic transmission.
Psychoactive drugs
__ is a plant-derived drug that blocks acetylcholine receptors on skeletal muscle cells, allowing surgeons to relax muscles during operations.
Curare
What types of disorders are treated with drugs that act on chemical synapses?
1) insomnia
2) anxiety
3) depression
4) schizophrenia
__ and __ bind to GABA receptors, enhancing the inhibitory action of GABA and allowing lower concentrations of GABA to open Cl⁻ channels more effectively.
1) Barbiturates
2) benzodiazepines
a neurotransmitter, a chemical messenger in your brain. It slows down your brain by blocking specific signals in your central nervous system (your brain and spinal cord). It is known for producing a calming effect.
Gamma-aminobutyric acid (GABA)
__ mechanisms in synaptic signaling, mediated by Na⁺-driven symports, clear neurotransmitters from the synaptic cleft, and inhibiting these transporters prolongs the effect of the neurotransmitter, thereby strengthening synaptic transmission.
Reuptake
Prozac and similar antidepressants inhibit the reuptake of __, and some also inhibit the reuptake of __, increasing their availability in the synaptic cleft.
- serotonin
- norepinephrine
Advancements in understanding the molecular biology of ion channels may lead to the design of more __ __ drugs aimed at alleviating mental illness while minimizing side effects.
selective psychoactive
Neuromuscular transmission is initiated when a __ __ reaches the nerve terminal, causing __ of the presynaptic membrane and opening voltage-gated __ channels.
- nerve impulse
- depolarization
- Ca²⁺
In neuromuscular junction, the influx of __ into the nerve terminal, due to its high extracellular concentration, triggers the local release of acetylcholine by exocytosis into the synaptic cleft.
Ca²⁺
Acetylcholine binds to its receptors on the muscle cell membrane (sarcolemma), causing cation channels to open, leading to an influx of __ and a local __ of the muscle membrane.
- Na⁺
- depolarization
These cations in the neuromuscular junction are essential, with __ primarily involved in neurotransmitter release and __ in generating and propagating action potentials.
- Ca²⁺
- Na⁺
After the local depolarization of the muscle cell membrane, it opens voltage-gated Na⁺ channels and allows more Na⁺ to enter. It results in a self-propagating depolarization that generates an __ __ across the entire muscle plasma membrane.
action potential
The generalized depolarization of the muscle cell membrane activates voltage-gated Ca²⁺ channels in the __ __ (_-__), which are essential for muscle contraction.
transverse tubules (T-tubules)
During muscle contraction, activation of (1)__ in the (2)__ causes a mechanical change that opens Ca²⁺-release channels in the adjacent sarcoplasmic reticulum, allowing Ca²⁺ to flow from the SR into the cytoplasm. The sudden increase in cytosolic Ca²⁺ concentration leads to the contraction of the (3)__ in the muscle cell.
1) voltage-gated Ca²⁺ channels
2) T-tubules
3) myofibrils
A single neuron can receive inputs from __ of other neurons and form synapses with many more, integrating information from various sources before reacting.
thousands
Motor neurons receive both (1) __ __, which cause depolarization (__ postsynaptic potentials, EPSPs), and (2)__ __, which cause hyperpolarization (__ postsynaptic potentials, IPSPs). (What type of signal?)
1) excitatory signals; excitatory
2) inhibitory signals; inhibitory
(1)__ is a small depolarization in the postsynaptic membrane caused by neurotransmitter release at an excitatory synapse.
Excitatory postsynaptic potential (EPSP)
(1)__ is a small hyperpolarization in the postsynaptic membrane caused by neurotransmitter release at an inhibitory synapse.
Inhibitory postsynaptic potential (IPSP)
Individual EPSP is generally insufficient to trigger an action potential. The plasma membrane of most neurons contains a relatively low density of (1)__ channels, making an individual EPSP too small to trigger an action potential.
1) voltage-gated Na⁺
If multiple signals arrive simultaneously at several synapses, the total PSP in that area will be the sum of the (1)__, with IPSPs contributing negatively to the total.
individual postsynaptic potential or PSPs
Postsynaptic potentials or PSPs are transmitted over long distances within a neuron by spreading (1)__ and converge on the cell body, where the combined magnitude is encoded into the (2)__ : stronger stimulation leads to higher firing rates.
1) passively
2) frequency of action potentials
The __ __ encodes the intensity of stimulation into action potential frequency for long-distance transmission, rich in voltage-gated Na⁺ channels and various K⁺ channels.
axon hillock
What types of K⁺ channels are present at the axon hillock? (3)
1) delayed
2) rapidly inactivating
3) Ca²⁺-activated K⁺ channels
, each contributing to action potential firing and response modulation.
Delayed K⁺ channels open after an action potential, allowing K⁺ __(influx/efflux), which repolarizes the membrane and prepares it for the next action potential.
efflux
Ca²⁺ channels allow Ca²⁺ __(influx/efflux) during action potentials, while Ca²⁺-activated K⁺ channels open in response to increased __(what ion), making the neuron __ responsive to prolonged stimulation (adaptation).
- influx
- Ca²⁺
- less
__ __ is the decreased responsiveness to constant stimulation, allowing neurons to react sensitively to changes, which is crucial for sensory processing (e.g., feeling light touch while ignoring clothing pressure).
Neuronal adaptation
The diversity of ion channels contribute to neuronal function. Hundreds of genes encode various ion channels, allowing neurons to have unique combinations of channels that tailor their electrical behavior to specific tasks, enabling __ __ and __.
- complex computations
- responses
__ __ is the ability of individual synapses to strengthen or weaken based on their use, playing a crucial role in learning and memory.
Synaptic plasticity
__-__ __ (__) is a persistent increase in synaptic strength following high-frequency stimulation of a synapse, crucial for learning and memory. The hippocampus plays a key role in forming new memories. It is triggered when a presynaptic neuron fires while the postsynaptic membrane is strongly depolarized, often due to repetitive stimulation. This allows glutamate to bind to (2)__ receptors.
long-term potentiation (LTP)
2) N-methyl-D-aspartate (NMDA)
__ receptors mediate most excitatory postsynaptic currents, while __ receptors are crucial for LTP because they allow Ca²⁺ entry when glutamate binds and the membrane is depolarized.
- AMPA
- NMDA
__ receptors are permeable to Ca²⁺, which acts as a signaling molecule in the postsynaptic cell, initiating a cascade of changes that lead to LTP.
NMDA
During long-term potentiation (LTP), the number of __ receptors in the postsynaptic membrane increases, enhancing the cell’s sensitivity to glutamate.
AMPA
(1)__ is a long-lasting decrease in synaptic strength that reduces AMPA receptors in the postsynaptic membrane. Unlike LTP, it involves lower levels of Ca²⁺ and activates protein phosphatases.
long-term depression (LTD)
High Ca²⁺ levels activate protein kinases leading to (1)__, while moderate Ca²⁺ levels activate protein phosphatases leading to (2)__, demonstrating bidirectional control of synaptic strength.
1) Long-term potentiation (LTP)
2) Long-term depression (LTD)
__ receptors are involved in synaptic plasticity and learning beyond the hippocampus and are crucial for adjusting synaptic connections during nervous system development.
NMDA
A key feature of neurotransmitter effects beyond signal transmission is it can alter __ __ __, leading to lasting changes in synaptic transmission efficacy, which contribute to learning and memory.
intracellular mediator concentrations
The signaling events in long-term potentiation:
1) (1.1)__ (what molecule?) binds to (1.2)__ receptors on the postsynaptic membrane, opening their channels and allowing (1.3)__ (what ion?) influx, which begins to depolarize the postsynaptic membrane.
2) Partial depolarization removes the (2.1)__ (what ion?) block from (2.2)__-__ channels, allowing them to open when (1.1)__ is bound, which permits (2.3)__(what ion?) entry into the postsynaptic cell.
3) Increased (2.3)__ concentration induces the postsynaptic cell to insert new (1.2)__ receptors into the plasma membrane, enhancing the cell’s sensitivity to (1.1)__.
1.1) Glutamate
1.2) AMPA
1.3)Na⁺
2.1) Mg²⁺
2.2) NMDA-receptor
2.3) Ca²⁺
Photosensitive ion channels that open in response to light, originally evolved as sensory receptors in green algae. They contain a covalently bound retinal group that absorbs light, triggering a conformational change that opens an ion channel.
channelrhodopsins
__are light-activated cation channels, while __ is a light-driven proton pump.
- Channelrhodopsins
- bacteriorhodopsin
What technique is used to express channelrhodopsin in specific cell types?
Genetic engineering techniques
Researchers control neuronal firing using channelrhodopsins by __ __ at specific frequencies, researchers can activate channelrhodopsin and induce neurons to fire action potentials.
- flashing light
A technique that allows researchers to activate or inhibit specific neurons in living animals with spatial and temporal precision using light. It allows analysis of neurons and circuits underlying complex behaviors, including aggression and social interactions.
optogenetics
Give an example of how channelrhodopsins have been used in research
In a study, channelrhodopsin was expressed in aggression-related neurons in mice; activating these neurons with light caused aggressive behavior.
What are some other types of light-responsive ion channels and transporters developed after channelrhodopsins? (1)
channels that can rapidly inactivate specific neurons
Optogenetics considered revolutionary in neurobiology because it enables __ __ of neuronal activity, providing insights into the neural basis of __ and neurological __.
- precise manipulation-
- behavior
- functions
