Neuroscience 1 - Unit 1
How are each of the potentials different from one another?
-Action potentials occur more frequently to indicate intensity. -Receptor potentials amplitudes are graded in proportion to the magnitude of the sensory stimulus. -Synaptic potentials amplitudes vary according to the number of synapses activated, the strength of each synapse, and the previous amount of synaptic activity.
reversal potential at neuromuscular junction
0 mV -> potential where the EPC reverses
Sums of inputs depends on:
1. Timing 2. Mix of inhibitory and excitatory inputs 3. Relative synaptic strengths 4. Relative synaptic locations
Suppose you are recording a neuron's resting membrane potential. If you add KCl to the external medium, what will happen to the resting potential? Compare this to what will happen if you add the same amount of NaCl. What can be concluded from this comparison?
Adding KCl will cause the resting potential to become less negative. Adding NaCl to the external medium will have a small effect because membrane permeability to Na+ is low. We can conclude that the resting membrane potential is primarily due to/attributable to the product of K+ permeability.
How does Botox relax the muscles of our face and rid it of wrinkles?
Cleaves SNAP25 and synaptobrevin
connexon
In a gap junction, a protein channel linking adjacent animal cells.
_____________ generate voltage across the membrane whereas ____________ control the flow of ions and generate currents.
Ion pumps ion channels
Which transporters plays a key role in maintaining the concentration gradients of ions in the brain that are critical for generating electrical signals?
Na+/K+ ATPase pump
Inactivation ball
Plugs voltage gated sensor up during inactivation phase.
Active transport
against concentration gradient
In familial hemiplegic migraine, the underlying mutation in a calcium channel causes
the syndrome by some unknown mechanism.
If the distribution of EPP amplitudes has peaks at 0.4 mV, 0.8 mV, 1.2 mV, 1.6 mV, and 2.0 mV, what is the most likely amplitude of the MEPP?
0.4 mV
How many subunits of K+ does it take to make a voltage gated channel? What about Na+? Why?
4 for K+, 1 for Na+ because Na+ subunits are 4x as long as K+
Nernst equation
A mathematical formula that predicts the electrical potential generated ionically across a membrane at electrochemical equilibrium.
ligand-gated ion channel
A protein pore in the plasma membrane that opens or closes in response to a chemical signal, allowing or blocking the flow of specific ions.
Tetraethylammonium ions
Blocks the K+ currents without affecting Na+ current.
Tetrodotoxin
Blocks the Na+ current without effecting the K+ current.
whole-cell recording
Cytoplasm is continuous with pipette interior. Allows diffusional exchange between the solution in the pipette and the cytoplasm, producing a convenient way to inject substances into the interior of a "patched" cell.
Differences between electrical and chemical synapses.
Electrical: -fast, bidirectional -GAP junctions -allows for diffusion of ions -allows for diffusion of small proteins and signaling molecules Chemical -much more common -slower than electrical and usually unidirectional -NO exchange of cytoplasmic contents bc vesicles and NT -highly plastic in their response
Explain how myelin speeds the conduction of the action potential.
It limits the areas of action potential generation, a time-consuming process, to nodes of Ranvier.
Which ion is crucial to resting potential?
K+
Leaky Channels
Not voltage sensitive, use gradient built up by pump to allow K+ ions to diffuse WITH CONCENTRATION GRADIENT.
V Snares (on vesicle)
Synaptobrevin
T Snares (on target membrane aka pre synaptic)
Syntaxin SNAP 25
A neuron has received enough stimulation to fire an action potential; it also has been treated with TEA, a K+ channel blocker. Which outcome is possible?
The cell will initially depolarize, but repolarization will take much longer because it relies only on ion pumps.
What do microscopic and macroscopic Na+ currents have in common?
They represent a flow of many ions.
In a two-compartment model of a cell with a K+-permeable membrane and a 10-fold excess K+ in the inside compartment, the membrane potential is experimentally made more negative than the K+ equilibrium potential. How would K+ ions flow across the membrane?
They would flow from the outside compartment to the inside compartment.
cell-attached patch clamp
Tight contact between pipette and membrane. Allows experimental control of the membrane potential to characterize the voltage dependence of membrane currents.
Suppose you are recording action potentials from a neuron. How will the action potential be affected if you remove: a) Na+, or b) K+ from the external medium?
a) It will be suppressed; the rising phase will not occur. b) It will be more difficult to trigger because the resting potential of the neuron will become even more negative.
List the steps involved in chemical neurotransmission, beginning with the synthesis of neurotransmitter and ending with the response of the postsynaptic neuron.
a) Synthesis of the neurotransmitter b) Packaging of the neurotransmitter c) Delivery of the neurotransmitter to the presynaptic terminal (if neurotransmitter is synthesized in the cell body) d) Arrival of the action potential to the presynaptic terminal e) Influx of Ca2+ into the presynaptic terminal f) Fusion of the synaptic vesicles with the presynaptic membrane g) Release of the neurotransmitter h) Binding of the neurotransmitter to its receptor on the postsynaptic membrane i) Response of the postsynaptic membrane or cell, which depends on the particular transmitter and receptor
A scientist wishes to develop a new drug that prevents synaptic communication via neuropeptides but not small molecule neurotransmitters. Which mechanism would be a good target for his drug? a. Disruption of axonal transport b. Blocking of voltage-gated calcium channels c. Disruption of V-SNARES d. Blocking of voltage-gated sodium channels e. Increasing levels of synaptotagmin
a.
The capability of a nerve terminal to rapidly and dramatically produce very large changes in calcium levels is most dependent on the a. presence of calcium-selective ion channels. b. enormous gradient of calcium across the membrane. c. fact that calcium is a positively charged ion. d. fact that calcium is a divalent cation. e. All of the above are essential for producing large, rapid concentration changes.
b.
When a muscle fiber is held at a voltage of 0 mV at the neuromuscular end plate, acetylcholine no longer produces a current because a. the acetylcholine receptor channels all close instantly at 0 mV. b. an influx of sodium is balanced by an equal efflux of potassium. c. the membrane conductance for each permeant ion is 0 at 0 mV. d. at 0 mV, the potassium ions lodge in the receptor channel and block the influx of sodium. e. the Nernst potentials for both sodium and potassium are 0 mV in muscle fibers.
b.
Which feature of an electrical synapse allows synchronizing the electrical activity of multiple neurons?
bidirectional transmission of electrical signals
Miniature end plate potentials, or MEPPs, are produced
by spontaneous release of neurotransmitter.
Summation
determines if all the synaptic inputs result in action potential(s) in the postsynaptic cell
The TRP ion channel family includes channels responsive to
heat and cold.
inhibitory signals
prevents post synaptic neuron from firing an action potential (it hyperpolarizes)
The current flowing through individual ion channels
reflects the passage of thousands of ions per millisecond.
Small-molecule neurotransmitters are _______ for _______.
taken back into the presynaptic terminal; reuse
Phasic Firing
Transient firing (lasting a short period of time) of action potentials in response to a prolonged stimulus; the opposite of tonic. -Cross-inhibitory network -Intrinsic resting potential oscillation (for example, through Ca++ activated K+ channels)
True or false. The positive and negative currents of the cell refer to the direction of the movement of ions, not the actual charge of the current.
True
True or False: Receptor potential and synaptic potential can become action potentials if not already labeled as a graded potential.
True - Just have to reach threshold.
Co transporters
Utilize the ion gradient from ion pumps to push ion UP their concentration gradient. MOVE IONS THE SAME WAY ACROSS THE MEMBRANE.
Exchangers (antiporters)
Utilize the ion gradient from ion pumps to push ions UP their concentration gradient. MOVE IONS IN OPPOSITE WAYS ACROSS THE MEMBRANE.
Ohm's Law
V = IR V = Voltage I = Current R = Resistance
Relate each variable of Ohm's law to what it represents in a neuron.
V = voltage across membrane I = flow of ions (movement) R = resistance to ion flow
What is the difference between Hodgkin and Huxley's voltage clamp method versus the patch clamp method?
Voltage clamp only allows for the macroscopic current of the cell, meaning it measures the current flowing through thousands of voltage gated channels. Patch clamp allows for the microscopic current of the cell, meaning it measures the current flowing through an individual channel.
What evidence indicates that EPPs are composed of MEPPs?
Experiments using Ca2+ and curare in the study of acetylcholine release at the neuromuscular junction led to the discovery of quantal fluctuations in the amplitude of EPPs. The amplitude of the smallest EPPs is similar in size to that of a single MEPP, and increments in the EPP response occur in units about the size of single MEPPs.
Synaptotagmin
Neither a V Snare or T Snare. Ca2+ sensor. What senses the influx and drives the SNARE complex together.
Receptor Potential
The membrane potential change elicited in a receptor neurons during sensory transduction. - charge but more + than resting potential -short range
How would application of an intracellular Ca2+ chelator affect the function of a synapse? a. It would increase the magnitude of postsynaptic potential. b. It would decrease the magnitude of postsynaptic potential. c. It would eliminate the postsynaptic potential but have no effect on presynaptic potential. d. It would eliminate the postsynaptic potential and Ca2+-dependent vesicle fusion. e. It would eliminate the presynaptic Ca2+ current but have no effect on the postsynaptic potential.
d.
Which statement about EPSPs in the central nervous system is true? a. They are much larger than end plate potentials. b. the istance between inputs does not affect the ability of EPSPs to summate c. the time between inputs does not affect the ability of EPSPs to summate d. Their effect in the central nervous system can be nullified by IPSPs. e. They can be hyperpolarizing.
d.
Presynaptic and postsynaptic neurons that form _______ synapses are connected via _______.
eletrical; gap junctions
The K+ channel is made up of ____________, each of which contains helical membrane-spanning domains with a ___________ between them.
four subunits; pore loop
reversal potential
the membrane potential at which there is no net (overall) flow of that particular ion from one side of the membrane to the other
A patient presents with migraines that usually last about 48 hours and are accompanied by vomiting. Two of his immediate relatives show similar symptoms. Which ion channel would you expect to be dysfunctional in this patient?
voltage-gated calcium channel
A synapse may be inhibitory or excitatory depending on...
where the Reversal Potential is relative to the threshold potential.
Structures that form the voltage sensors of K+ channels
are embedded in the cell membrane.
The resting potential of a cell is negative because
at rest there is an excess of K+ inside the cell, and the membrane is permeable chiefly to K+.
How would application of a Ca2+ channel blocker affect the function of a synapse? a. It would increase the magnitude of postsynaptic potential. b. It would decrease the magnitude of postsynaptic potential. c. It would eliminate the postsynaptic potential but have no effect on presynaptic neuron. d. It would eliminate the postsynaptic potential and the presynaptic Ca2+ current. e. It would eliminate the presynaptic Ca2+ current but have no effect on the postsynaptic potential.
d.
List five major stimulus types that can gate (open or close) various kinds of ion channels.
Voltage, ligand, mechanical force, temperature, and light
Name the two main proteins involved in endocytosis and describe their roles in the process.
Clathrin molecules assemble on the plasma membrane, forming domelike coated pits that initiate budding. These domes increase the curvature of the membrane until it becomes a vesicle-like structure that is connected to the plasma membrane by a narrow stalk. Dynamin forms a coil around this stalk and subsequently pinches off the coated vesicle.
What is the primary pathophysiological mechanism associated with multiple sclerosis?
Immune response within the nervous system.
Which statement accurately describes the difference between bacterial and mammalian channels that are selectively permeable to k+?
Mammalian K+ channels have four additional structures that act as voltage sensors.
Describe the difference in conduction of passive electrical signals and action potentials by excitable cells.
Passive electrical signals attenuate over distance, action potentials are actively regenerated in excitable cells (opening of Na channels)
Briefly describe how each of the following experimental approaches and tools can be used to study ion channels: Patch clamping Toxins
Patch clamping - can be used to evaluate current flowing through a single channel Toxins - used to modify or suppress the function of certain in channels during studies
Which statement describes one of the features of Hodgkin and Huxley's mathematical model?
The action potential can be reconstructed based entirely on the time course and amplitudes of the ionic conductances.
Summarize experimental evidence that synaptic vesicles are recycled in the axon terminal.
The enzyme horseradish peroxidase (HRP) was applied to the synaptic cleft at a frog neuromuscular junction while the neurons were stimulated. Movement of the enzyme was followed by observation under the electron microscope. HRP was first visualized in coated vesicles, then in endosomes, and finally, in newly-assembled synaptic vesicles.
Overview of how neurotransmitters are released at the chemical synapse.
1. Action potential arrives at presynaptic bouton, causing membrane to depolarize, allowing Ca2+ channels to open. 2. Calcium flows into the neuron and synaptotagmin senses this and drives the SNARE complex to fuse. 3. The vesicle membrane and presynaptic membrane become fused, neurotransmitter spills into the synaptic cleft. 4. Once there, it binds to receptors on the post synaptic membrane. 5. This can either be excitatory or inhibitory depending on the receptor type.
Classify Ion Pumps, Voltage Gated Channels, Leaky Channels, Co transporters, exchangers as either active or passive transport.
Active Transport: Ion Pump, Co transporter, Exchanger Passive Transport: Voltage gated channels, Leaky channels
What is an end plate potential?
Change in membrane potential of a muscle cell after a neuron depolarizes and spreads it to the muscle cell via the neuromuscular conjunction. It is below threshold. If it reaches threshold then an action potential can occur.
Depolarization
Displacement of a cell's membrane potential toward a less negative value.
Hyperpolarization
The displacement of a cell's membrane potential toward a more negative value.
What is the main function of SNARE proteins?
To bring the presynaptic and vesicle membranes together by twisting them close.
Voltage gated channels
Voltage sensitive, use gradient built up by pump to allow Na+ or K+ ions to diffuse WITH CONCENTRATION GRADIENT AT CERTAIN VOLTAGES.
positive current indicates...
a movement of positive ions out of the cell (K+ during action potentials)
The amplitude of the action potential of a given neuron is
always the same.
Studies of the ionic basis of the action potential in giant squid axon found that
decreasing sodium outside the cell decreases the size of the action potential.
inside out recording
exposed to air & cytoplasm (intracellular) domain/surface is accessible allowance to change the medium to which the intracellular surface of the membrane is exposed particularly valuable when studying the influence of intracellular molecules on ion channel function
Positive current indicates a movement of positive ions out of the cell, or ____________________, whereas negative current indicates a movement of positive ions into the cell, or ____________________.
hyperpolarization depolarization
large dense core vesicles
typically contain larger complex neuropeptide transmitters
Goldman equation
used in cell membrane physiology to determine the reversal potential across a cell's membrane, taking into account all of the ions that are permeant through that membrane
The link between electrical and chemical activity is ________.
Ca2+
Which structure is found exclusively at an electrical synapse?
Connexon
Which ion is transported down its concentration gradient by transporters?
Na+
During the overshoot phase of an action potential, membrane potential briefly reaches a value near ________ mV.
+50
Hodgkin and Katz discovered that the resting membrane potential changes by _________ mV per tenfold change in K+ concentration.
+58
How many connexin subunits form one complete synaptic channel?
12
end plate current (EPC)
A macroscopic postsynaptic current resulting from the summed opening of many ion channels; produced by neurotransmitter release and binding at the motor end plate.
Which structural features of K+ channels account for: a) ion selectivity, b) voltage sensitivity, and c) ion conductance?
A) Selectivity filter: pore loops create a pore too small for larger ions but too large for smaller ions to be stabilized B) Voltage sensor C) Pore
Which symptom(s) is characteristic of patients with multiple sclerosis?
Abnormal somatic sensations due to lesions of somatosensory pathways
Explain the regenerative property of the action potential.
During the action potential, an active inward current produced by depolarization spreads passively inside the axon and depolarizes an adjacent membrane region. This results in generation of another action potential in this adjacent region, and the cycle repeats; hence, the regeneration of the action potential.
What is the mechanism of action of the different active transporters? Explain the differences between the following types of active transporters: ATPase pumps, antiporters, and co-transporters. Provide an example of each.
All active transporters must be able to move ions across the membrane against their concentration gradient. The ATPase pump moves ions across the membrane using energy derived from ATP hydrolysis. Example: Na+/K+ ATPase pump. An ion exchanger moves ions by using energy derived from electrochemical gradient of other ions. There are two types of ion exchangers: antiporters and co-transporters. Antiporters transport ions in opposite directions. Example: Na+/H+ exchanger. Co-transporters transport ions in the same direction. Example: Na+/K+/Cl- co-transporter.
Which of the following is false regarding the K+ voltage gated channel subunit? A. The voltage sensor is what opens and closes the channel according to the voltage changes in the cell. B. The calcium sensor is located on the amino end of the subunit and is present in every K+ channel subtype C. The voltage sensor is the 4th helix of the subunit D. The pore domain is what specifies the selectivity of the channel to a particular ion E. All of the above are correct
B.
Compare the responses of voltage-gated Na+ and K+ channels to depolarization.
Both types of channels open in response to depolarization; however, depolarization inactivates Na+ channel for a period of time. In contrast, K+ channels are not inactivated.
What is significant about the quantal nature of MEPPs?
Each MEPP is evoked by the release of a single packet of neurotransmitter (synaptic vesicle) from the presynaptic terminal.
What would occur if the ATPase pumps in a neuron stopped functioning?
Concentration gradients would not be maintained across the membrane.
small clear-core vesicles
Contain simpler, smaller neurotransmitter molecules.
Ligand-gated K+ channels
Distinguished by ligand-binding domains on their intracellular surfaces that interact with second messengers. In many causes, K+ channels are activated by Ca2+.
Compare and contrast electrical and chemical synapses.
Electrical synapses allow for fast signal transmission and bidirectional communication between cells connected via an electrical synapse. Chemical synapses allow for a broad range of postsynaptic responses, but the transmission is slower in chemical synapses than electrical synapses.
inside-out recording
Expose cytoplasmic domain to air and makes cytoplasmic domain accessible. Valuable when studying the influence of intracellular molecules on ion channel function.
What is the source of the quanta make up the EPP?
Fusion of individual synaptic vesicles with the plasma membrane.
Which of the following statements correctly explains why a Na+ ion cannot fit inside of a K+ voltage gated channel? I. The selective pore uses carbonyl groups to strip the hydration shell of an ion for it to pass and there is more water surrounding the K+ ion than the Na+ II. The Na+ ion is slightly smaller than the K+ ion and cannot fit into the selective pore III. The voltage sensor of the Na+ channel is different than that of the K+ channel
II only
How does the voltage sensitivity of K+ conductance contribute to the action potential?
It enables the falling phase, allowing the action potential to finish running its course. Depolarization slowly activates the voltage-dependent K+ conductance, causing K+ to leave the cell and repolarizing the membrane potential toward EK. The hyperpolarization of the membrane potential causes the voltage-dependent K+ conductance to turn off, allowing the membrane potential to return to its resting level.
Describe the roles SNAREs and synaptotagmin in neurotransmitter secretion. Which one is key in the initiation of transmitter release by Ca2+?
NSF and SNAPs: prime synaptic vesicles for fusion SNAREs (synaptobrevin (vesicle), syntaxin(pre-synaptic), SNAP-25 (pre-synaptic)): link vesicle with the presynaptic membrane Synaptotagmin: binds calcium to trigger fusion of vesicles with the presynaptic membrane Synaptotagmin is key in the initiation of transmitter release.
What is the net charge trasnported by one cycle of the Na+/K+ ATPase pump?
One positive charge leaves the cell.
Provide scientific evidence of the existence of chemical synapses.
Otto Loewi proved that electrical information can be transferred from the vagus nerve to the heart by means of a chemical signal, which was later shown to be acetylcholine.
Which technique would you use to study the effects of the extracellular environment on ion channel activity?
Outside-out patch clamp
What is patch clamping? Explain how it can be used to show that properties of voltage-sensitive Na+ and K+ channels are responsible for the action potential.
Patch clamping is a technique in which a recording pipet is used to grip a cell membrane and record the electrical potential or flow of ions through one ion channel. The patch clamp method allows experimental control of the membrane potential, and it can be used to characterize the voltage dependence of membrane currents. It allows measuring minute electrical currents such as those originating from a single ion channel.
Which statement correctly differentiates between the passive and active current in a myelinated axon?
The active current flows only in the nodes of Ranvier, unlike the passive current which spreads through myelinated axon.
outside-out recording
The pipette is retracted while it is in the whole-cell configuration, the membrane patch produced has its extracellular surface exposed. Optimal for studying how channel activity is influenced by extracellular chemical signals such as neurotransmitters. 1. Retract pipette 2. Ends of membrane anneal 3. Extracellular domain accessible
There are nearly 100 genes for K+ channels. What value might there be in such variation?
The value of a large number of genes, which fall into several distinct groups of channel proteins, is that several different K+ channel proteins can be produced from them, each different from one another in function, permitting variation in cell function, such as the different signaling properties found among neurons.
What is the voltage clamp method?
The voltage clamp method allows characterization of permeability changes as a function of membrane potential and time.
Explain how Hodgkin and Huxley used the voltage clamp method to show that changes in permeability to Na+ and K+ underlie the action potential.
Using the giant axon of a squid, they showed that depolarization is followed by transient inward current and lasting outward current. This inward current does not flow if the membrane potential is clamped at +52 mV, the equilibrium potential for Na+, indicating that it is attributable to Na+ permeability. They also removed Na+ from the extracellular medium and found that this reverses the polarity of the early Na+ current but has no effect on the delayed lasting current. Using radioactive K+, they confirmed the involvement of K+ in the delayed current.
The technique that provides the most direct information about the physical, three-dimensional structure of ion channels is
X-ray crytallography.
Do unmyelinated axons generate and propagate action potentials?
Yes
"A rise in presynaptic Ca2+ is necessary and sufficient for neurotransmitter release." Which experimental evidence a) supports the claim that Ca2+ is necessary, and b) supports the claim that Ca2+ is sufficient?
a) Presynaptic microinjection of calcium chelators prevents presynaptic action potentials from causing neurotransmitter secretion. b) Microinjection of Ca2+ into presynaptic terminals triggers neurotransmitter release even in the absence of presynaptic action potentials.
Provide two lines of evidence that suggest that neurotransmitters are released from synaptic vesicles.
a) Studies by Katz et al. showed that acetylcholine is released in packets, each equivalent to a MEPP. b) Studies by Heuser, Reese et al. revealed a correlation between the number of fused vesicles on an electron microphotograph and the number of quanta in the EPP produced.
Which statement is a common, defining feature of membrane-bound active ion transporters? a. All are electrogenic. b. All transport two or more different ions. c. All catalyze the conversion of ATP to ADP. d. All are able to move at least one ion against its concentration gradient. e. All move sodium across the membrane.
a.
You conduct a voltage clamp experiment in which you hold the presynaptic terminal of a glutamatergic neuron (a neuron that releases glutamate) at 0 mV. When you treat the terminal with TTX, an inward current is recorded. Which ion and ion channels are responsible for the current you observe? a. Calcium; voltage-gated calcium channels b. Sodium; voltage-gated sodium channels c. Potassium; voltage-gated potassium channels d. Calcium; ligand-gated non-specific cation channels e. Sodium; ligand-gated non-specific cation channels
a.
The decrease in size of individual quanta observed in familial infantile myasthenia is consistent with the observation of a. fewer calcium channels in the presynaptic terminals compared with healthy controls. b. a greater rate of spontaneous exocytosis depleting the size of the vesicle pool, than in healthy controls. c. smaller synaptic vesicles compared with healthy controls. d. a change in the sensitivity of the calcium release mechanism compared with healthy controls. e. a loss of all ACh receptors at the neuromuscular junction.
c.
The most important factor determining whether a receptor-operated ion channel is inhibitory or excitatory is a. the ligand-binding properties of the receptor. b. whether the permeant ion is positively or negatively charged. c. whether the permeant ion's reversal potential is positive or negative to threshold. d. the number of different ions that can pass through the receptor. e. None of the above
c.
Which of the following was observed in studies measuring the efflux of radioactive sodium from the squid giant axon? a. Dramatic increase of efflux during a brief train of action potentials b. Sharp drop in efflux when intracellular potassium was removed c. Dependence of efflux upon the presence of ATP d. Decrease of efflux when ATP synthesis was increased e. No recovery when potassium or ATP was restored.
c.
Gap junctions may exhibit all of the following features except a. the ability to pass small metabolites, including some second messengers. b. the ability to pass electrical current bidirectionally. c. the ability to pass electrical current unidirectionally. d. the ability to amplify small incoming electrical signals into large regenerative potentials. e. the ability to synchronize the activity of populations of nerve cells.
d.
Which step of peptide neurotransmitter processing takes place in the presynaptic terminal? a. Synthesis b. Packaging c. Transport d. Release e. Degradation
d.
Which treatment would prevent the release of neurotransmitter from the presynaptic terminal? a. Potassium channel blocker b. Acetylcholinesterase c. Monoamine oxidase inhibitor d. A toxin that cleaves synaptobrevin e. AMPA antagonist
d.
Even _______________ inputs can be inhibitory, as long as the reversal potential is below _______________ _________________.
depolarizing; threshold potential
By which proposed molecular mechanism does Ca2+ promote fusion of synaptic vesicles? a. By binding to synapsin b. By binding SNARE proteins to the complex formation c. By binding to SNARE proteins after the complex formation d. By binding to synaptotagmin and promoting formation of the SNARE complex, which facilitates fusion e. By binding to and inducing changes in synaptotagmin that cause the plasma membrane to curve, facilitating fusion
e.
To date, which observation is not part of the experimental evidence favoring the vesicular release hypothesis of neurotransmission? a. Fixed size of MEPPs b. Quantized distribution of events occurring at the neuromuscular junction c. Visualization of synaptic vesicles using electron microscopy d. Correspondence between a vesicle's acetylcholine content and MEPP size e. Visualization of acetylcholine molecules diffusing out of the neck of the membrane-fused vesicle
e.
What determines if a neurotransmitter is excitatory or inhibitory? A. If it is a neuropeptide, it is excitatory B. It depends on the ions that the target receptor is permeable to. C. It depends on the size of the neurotransmitter molecule D. It depends on the reversal potential of the target receptor E. B and D
e.
Which observation would indicate a role for calcium in transmitter secretion? a. Observation of presynaptic depolarizing currents after blockade of sodium channels b. Voltage clamp experiments showing voltage-gated calcium channels in the presynaptic terminal c. Induction of transmitter release by injection of calcium into the presynaptic terminal d. Blockade of transmitter release by injection of calcium blocker into the presynaptic terminal e. All of the above
e.
Which statement about postsynaptic currents at the neuromuscular end plate is false? a. Depolarizing currents can be recorded from outside-out patches of the postsynaptic membrane. b. Individual channels tend to stay open for no more than a few milliseconds. c. Acetylcholine can induce openings of ligand-gated ion channels. d. The end plate potential is due to the opening of thousands or millions of channels. e. The end plate channels show a regenerative opening pattern that propagates an action potential along the length of the muscle fiber.
e.
Which substances diffuse through connexin channels between pre- and postsynaptic neurons? a. Ions b. Second messengers c. Small proteins d. ATP e. All of the above
e.
At -10 mV, end plate current is _______ in amplitude and directed _______.
small; inward
Electrogenic
producing a change in the electrical potential of a cell
The _______ most directly affects the rate of information processing within the central nervous system.
propagation speed of action potentials
What two proteins regulate the SNARE porteins and organize them into the correct conformation for membrane fusion?
NSF and SNAP
If the resting potential of a neuron is -90 mV, which ion (K+ or Na+) has a greater driving force?
Na+
Quantal content
Number of effective vesicles released in response to a nerve impulse (action potential).
Quantal size
Number of neurotransmitter molecules in a vesicle.
Voltage sensor
Opens or closes the channel depending on voltage.
Discuss, in detail, how the pore domain is selective for a certain ion, and why a Na+ ion cannot fit in a K+ voltage gated channel.
Pore domain has a selective pore, and it uses carbonyl groups to strip the hydration shell of an ion for it to pass. There's more water surrounding the Na+ ion than the K+ ion, so Na+ doesn't fit correctly into the pore. There are carbonyl groups inside the pore and the ion has to fit just right for it to pass, but Na+ is smaller than K+ so it won't fit correctly nor pass.
Ion channels
Proteins that allow only certain kinds of ions to cross the membrane in the direction of their concentration gradients.
What classic experiment helped us understand how neurotransmitters work at the chemical synapses of neurons?
Put two hearts in two different chambers that were connected with a tube. They stimulated the vagus nerve to heart 1 and the heart rate decreased. The second heart's rate decreased as well, indicating that there was something in the solution (neurotransmitter) that was causing the second heart rate to decrease even though it was no stimulated.
Nernst equation
Relates the equilibrium potential of an ion to its intra- and extracellular concentrations.
Steps of Action Potential
Rest: Leaky K+ channel and Na+/K+ pump are in action. Rising Phase: Initial depolarization brings to threshold. Once reached, voltage gated Na+ channels open. Falling Phase: K+ voltage gated channels open and Na+ channels inactivate. Undershoot (Refractory): K+ voltage channels remain open, Na+ still inactivated. "Return to rest": Both voltage gated channels begin to close.
How are small clear core and large dense core vesicles are different?
Small clear core: -enzymes needed to synthesize neurotransmitter are made in cell body -these are transported to the presynaptic bouton via slow axonal transport -the actual neurotransmitters are synthesized at the presynaptic bouton -tend to hang out lower on the bouton, so local Ca2+ influx will trigger release of these -neurotransmitter recycled Large dense core: -precursors and enzymes and actual neurotransmitters are all made in the cell body -these are then transported to the presynatpic bouton via fast axonal transport via microtubules -tend to hangout further up onthe bouton, so it requires much more Ca2+ influx for these to be released -diffuses away and is typically degraded by a proteiolytic enzyme
What channels/pumps does tetrodotoxin block? What happens when it blocks them? Does it block macroscopic current of this ion or the microscopic current? Or both?
Sodium, the depolarization becomes prolonged, the threshold becomes raised, makes it harder to reach threshold. It affects both, because microscopic is the basis for macroscopic current.
Tonic Firing
Sustained activity in response to an ongoing stimulus; the opposite of phasic. -Resting potential above threshold -Could be driven by another tonicaly-firing excitatory neuron -Modulatory input raising resting potential above threshold
What do we mean when we discuss the "driving force" of an ion?
The "driving force" of an ion is the push an ion has on cell voltage due to its influx or eflux out of the cell. -Different between membrane potential and equilibrium potential for the ion flowing through conductance (Nernst potential).
Which factor is important in determining the membrane potential when there are multiple permeant ions?
The concentration gradient of the individual ionic species and the permeability of the membrane to the individual ionic species.
What could be said about the conductance of K+ with high amounts of tetraethylammonium or dendrotoxin?
The conductance is low.
Why is it that there is a response in current from the depolarization stimulus but not the hyperpolarization when the voltage clamp method is used.
The depolarization stimilus causes an influex of Na+ into the cell and K+ out of the cell to get the membrane potential back to resting potential. Hyperpolarization does not cause the influx of Na+ that triggers the threshold to signal action potential to occur.
Synaptic Potential
The electrical signal associated with communication between neurons at synaptic contacts. - charge but more + than resting potential -short range
Action Potential
The electrical signal conducted along axons (muscle fibers) by which info is conveyed from one place to another in the nervous system. + charge -long range
Resting Potential
The inside-negative electrical potential that is normally recorded across all cell membranes.
What is the patch clamp method, and what did it allow researchers to do? How does it work?
The patch clamp method allowed researchers to look at single ion channels rather than a collective current from them across the cell to examine the current that flows through them individually. It works by inserting an electrode into the cell and making a very negative voltage so that the channels are closed, then blocking either the sodium or potassium ones depending on which you want to study, then introducing a depolarizing current into the cell and recording the individual response of a channel to that depolarization.
membrane potential (mV)
The potential inside a cell membrane measured relative to the fluid just outside; it is negative under resting conditions and becomes positive during an action potential.
Which process(es) underlie(s) the refractory period?
The slow time course of turning off K+ conductance activation and the persistence of Na+ conductance inactivation.
What is electrochemical equilibrium?
The state of balance between the concentration and electrical gradients at which there is no net flow of charge or ions.
After the neurotransmitter is dumped into the synaptic cleft, the neurotransmitter fuses with the receptor on the synaptic neuron. What makes the signal excitatory or inhibitory on the post synaptic cell?
The type of receptor on the post synaptic cell.
Ions Pumps
Move ions across the membrane AGAINST THEIR CONCENTRATION GRADIENTS. Use ATP.
What ion is responsible for the transient inward current (negative current)? What about the delayed outward current (positive current)?
1.) Na+ 2.) K+
What is the magnitude of a typical neuron's resting membrane potential? Why do neurons and other cells have a negative resting membrane potential?
A typical neuron's resting membrane potential is approximately -65 mV. It is negative because resting membrane is permeable mainly to K+, and there is a concentration gradient for K+ across the plasma membrane with roughly a 13-fold excess of K+ inside the cell.
Active Transporters
Actively move ions into or out of cells against their concentration gradients.
The voltage clamp method allowed neuroscientists to fully understand the action potential. How does it work?
An experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. -Allowed experimenters to control membrane potential and simultaneously measure the underlying permeability changes.
Exchangers and cotransporters use the gradient that ion pumps generate and are considered active transport. Voltage gated channels (and the leaky channels) also use the gradient generated by the ion pumps, but aren't considered active transport, they're considered passive. Why is this?
Because voltage gated and leaky channels transport ions WITH their gradient, not against.
True or false. Correct if false. The Na+ ion has a voltage gated channels at the presynaptic bouton that open when the area is depolarized from an incoming action potential. The local influx of the Na+ ion is what drives the vesicles to fuse to the membrane and the pre and post synaptic membranes to fuse to each other.
Ca2+, not Na+
Graded Potentials
Changes in membrane potential that vary in size, as opposed to being all-or-none. ex. receptor potential synaptic potential
Which statement regarding membrane potential and equilibrium potential is true?
Equilibrium potential is affected by the concentration and electrical gradients of one ion; membrane potential is affected by gradients of all ions.
True or False: Only voltage gated Na+ channels respond to a depolarization of a cell.
False - The voltage gated Na+ channels respond rapidly to a depolarization of a cell white K+ has a pronounced delay.
What is the concentration gradient of Ca2+ at resting potential?
High concentration outside Low concentration inside
Suppose a water-filled aquarium is divided into two compartments by a membrane that is impermeable to all ions. If KCl is added to one compartment, what will happen to the distribution of K+ and Cl-? Will there be a potential difference between the two compartments? What will happen to the membrane potential if the membrane suddenly becomes selectively permeable to K+ (but not to Cl-)?
If KCl is added to one compartment, nothing will happen because the membrane is impermeable. There will not be a potential difference between the two compartments. If the membrane suddenly becomes selectively permeable to K+ (but not to Cl-), it will reach equilibrium potential for K+.
Rearranged equation of Ohm's law for current
Iion = gion (Vm - Eion) Iion = ionic current gion = membrane conductance (similar to membrane potential, are channels opened or closed) Vm = membrane potential Eion = equilibrium potential for the ion flowing through condictance (Nernst potential)
Which current is produced in response to a hyperpolarizing stimulus in a giant axon of a squid?
Inward capacitive current
Which statement about electrochemical equilibrium is true?
It occurs when the potential across the membrane exactly offsets the concentration gradient.
Which statement about passive current involved in action potential propagation is most accurate?
It opens voltage-dependent Na+ channels in the adjacent region of axon.
Which voltage gated channel is the largest and most diverse class of voltage gated channel? Why?
K+, because it mainly controls the resting potential because the Nernst potential (Ek) is closest to rest, therefore controls the threshold of the neuron, which then determines whether an action potential will fire. There is a diversity of threshold potentials, so that means there must be a greater diversity of K+ channels.
What is a miniature end plate potential (MEPP) and what did the experiment with them show?
MEPP are spontaneous changes in the muscle cell potential in the absence of an action potential. They occurred in the absence of presynaptic stimulation. They showed that neurotransmitters release isn't a secretion at one time, but packets of a specific size.
Examples of resistance at "macroscopic" and microscopic level:
Macroscopic: myelination of axon Microscopic: voltage-gated ions
How could you be sure which ion is responsible for the negative current? What experiment could you design?
You could remove the external Na+. It would cause the early current to reverse its polarity and become an outward current at a membrane that gave rise to an inward current when external Na+ was present. Demonstrates convincingly that the early inward current measured when Na+ is present in the external medium must be due to Na+ entering the neuron.
negative current indicates...
a movement of positive ions into the cell (Na+ during action potentials)
Subthreshold current injected into an axon flows __________ along the axon and _________ with distance from the site of injection.
actively; decays
excitatory signals
causes post synaptic neuron to fire an action potential (it depolarizes it)
The _______________ gradient deals with the positive and negative aspect of the cell, whereas the _________________ gradient deals with the concentration of the different ions. These two counterbalance each other so that the cell does not get too negative. How?
electrical chemical The Na+/K+ pump produces and maintains the transmembrane gradients of Na+ and K+, while other transporters are responsible for the electrochemical gradients for other phsiologically important ions, including Cl-, Ca++, H+.
cell-attached recording
mild suction & tight contact between pipette and membrane allows experimental control of the membrane potential to characterize the voltage dependence of membrane currents membrane still intact, single cell
whole cell recording
record current from the whole membrane Break the membrane, but cytoplasm still continuous with pipet. Whole cell.
The squid giant axon is useful in neuronal studies because
the cytoplasm in the axon can be extruded, thus allowing studies of its composition.
The voltage clamp apparatus has _________ electrodes, and the ___________ compares the actual membrane potential with the command potential.
three; amplifier
passive transport
with concentration gradient