Exam 1

In the cell's hyperpolarized state, the __________ (what protein) uses energy to reset the ion concentrations and restore resting membrane potential.

Na+/K+ pump

The _____________ only works in the presence of both Na+ and K+, as well as ATP. If you don't have any one of those three components, you're not gonna get ion movement w/ the pump!

Na+/K+ pump

What happens to a neuron when you reduce external [Na+]?

The amplitude and rate of rise in the AP is reduced - probably because there's less Na+ to rush into the cell to cause an AP; this recovers when the Na+ is replaced

What prevents the action potential from traveling backwards?

the refractory period

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?

Block axonal transport, since neuropeptides are produced in the soma and need to make their way to the axon terminal

(Inhibitory/Excitatory) synapses are usually on soma and involve the NT GABA while (inhibitory/excitatory) synapses are usually on dendrites and involve the NT glutamate.

Inhibitory; excitatory

The resting membrane potential of a neuron is dependent on the concentration of what ion?

K+

Recall: the equilibrium potential for (Na+/K+) is -58 mV while the equilibrium potential for (Na+/K+) is +58 mV.

K+; Na+

True or False: If you injected Ca2+ into an axon terminal, you would still see vesicle docking and release even if Na+ channels were blocked b/c this process is purely dependent on Ca2+.

True. Ca2+ is SUFFICIENT for release of NTs to take place.

Voltage Clamp v. Patch Clamp

Voltage Clamp: manipulate membrane potential to measure current (ion flow); holding voltage steady to observe changes in current Patch Clamp: manipulate whole cell with current to measure membrane potential (voltage) or manipulate part of cell, such as an ion channel, to measure current through the ion channel

Describe the mechanism of activation for a) AMPA andn b) NMDA glutamate receptors.

a) AMPARs are ligand-gated ion channels. Once glutamate binds to the receptor, the channel opens to allow cations to enter the cell. b) NMDARs require both glutamate and glycine to bind, and they also require depolarization, enough to remove the Mg2+ plug in the channel. Once these requirements are met, the channel opens to allow cations to enter the cell. NMDARs often work in concert with AMPARs, as the faster-acting AMPARs cause the depolarization required by the NMDARs.

For vesicles to fuse w/ presynaptic membrane, this requires stimulation of the ____________ zone. If there's no stimulation, vesicles may just sit there, docked and waiting.

active

Goldman Equation

an equation that allows you to calculate membrane potential taking into account the fact that the cell is permeable to more than one ion (K+, Na+, Cl-, etc.)

Nernst Equation

an equation that allows you to predict the equilibrium membrane potential based on the concentration of a particular ion (assumes that the cell is permeable to this particular ion only)

capacitive current

automatic response in recording during voltage clamping; immediate response to a change in the membrane potential (you might see this at the very start and end of a stimulus)

synaptotagmin

binds to SNARE complex and waits for calcium to bind; once calcium binds, SNARE proteins change conformation and tighten around SNAREs; pushes 2 plasma membranes together => eventually results in vesicle fusion; calcium-dependent

Veratridine and aconitine are produced by a lily flower and the monkshood flower. Given that these toxins may result in seizures (but not instant death), what might their mechanism of action be?

blocking Na+ channel inactivation so channels remain open; cells are unable to return to their resting state = over-excitement

SNAREs

class of different proteins that are giant springs; one anchored in plasma membrane, another anchored in the vesicle; NOT calcium-dependent

EPP

end-plate potential Depolarization of the end plate (the area on the muscle cell where the axon synapses) *in NMJs (neuromuscular junctions)

post-synaptic density

indicates proteins and other stuff preparing to receive the NTs on the surface of the post-synaptic cell

The Cre/lox system is an example of an _____________ system, which means we can control WHEN and WHERE a gene is knocked out in the body!

inducible involves the expression of Cre recombinase, an enzyme that disrupts a gene on the loxP binding sites

List some factors that improve axon conductance (speed).

large diameter myelination (saltatory conduction)

synapsins

link together vesicles waiting on reserve in the presynaptic terminal; regulate how many vesicles are at the plasma membrane, docked and ready to go; calcium-dependent reserve pool Think: "snapping" like you're just hanging around, waiting, snapping to pass the time...

If you inject subthreshod level of current into an axon, you have (active/passive) current flow in the axon, and the amplitude of the potential responses (increases/decreases) as distance from the injection site increases.

passive; decreases (decays)

refractory period

period during an action potential when the neuron can NOT fire another action potential because Na+ channels are inactivated and the cell is hyperpolarized

A calcium chelator, which absorbs/attaches to calcium, would (cause/prevent) NT release at the presynaptic terminal.

prevent

clathrin triskelia

proteins that assemble together to form membrane coats involved in membrane budding during endocytosis

electrochemical equilibrium

state at which there is no net movement of a given ion across a semipermeable membrane and the concentration gradient is equal in magnitude to the electrical gradient

If looking for a neuron that expresses or uses a particular NT, what is a good target of interest?

the ENZYME that makes the NT of interest; look in presynaptic cells

command voltage

the desired voltage you set your membrane potential at in voltage clamping

How could you produce a 1:1 ratio for Na+/K+ (hint: what type of protein would you use)?

use an antiporter

fluid-mechanical theory of brain function

ventricles pump fluid around the body, leading to muscle movement; the body is a series of interconnected tubes, and fluid movement drives the movement of the body; attributed to Andreas Vesalius (1500s)

What are 4 staining methods used to visualize neurons?

1. Golgi stain: turns entire cell black; study overall cell morphology 2. fluorescent dyes: study overall cell morphology 3. enzymatic reaction identification: label specific cell type; ex: if you want to isolate cholinergic neurons, you inject an enzyme that is specific to a reaction/substrate you know is present in cholinergic neurons 4. cresyl violet RNA stain (aka Nissl stain): stains RNA in ALL cells in a tissue, labeling the nucleolus (but not the nucleus) as well as the ribosome-rich ER; dendrites and axons are NOT labeled; you can see the cell bodies, but you don't know anything about the processes (axons, dendrites, etc.); *good for determining cell density; you can image layers of the cortex and visualize the stratification and cell distribution

What are the 4 phases of the action potential?

1. Rising phase (Na+ enters cell and depolarization) 2. Overshoot phase (cell reaches peak depolarization and Na+ channels are inactivated) 3. Falling phase (K+ channels open and K+ leaves cell while the Na+ channels are all closed at this point; neuron cannot fire another action potential = absolute refractory period) 4. Undershoot phase (cell is temporarily hyperpolarized because so much K+ has left the cell; cell reaches a point where it COULD fire another action potential if it had a strong enough stimulus and depolarization = relative refractory period) Neuron returns to resting membrane potential

Outline the steps for endocytic budding (using clathrin and dynamin).

1. Vesicle fuses w/ presynaptic terminal, adding to membrane surface area 2. Clathrin triskelion assembles around membrane, pulling up on plasma membrane 3. Forms coating around vesicle, and dynamin pinches off vesicle/clathrin complex from membrane 4. Actin guides complexes to different locations within the cell 5. Uncoating of the vesicle takes place 6. Vesicles fuse together inside cell in the endosome

List some different methods for imaging the whole brain (ex: X-ray).

1. X-ray 2. electroencephalography (EEG) 3. transcranial magnetic stimulation (TMS) 4. CAT scan (computerized axial tomography) aka CT scan 5. Magnetic Resonance Imaging (MRI) 6. Functional Magnetic Resonance Imaging (fMRI) 7. Magnetoencephalography (MEG)

What are two methods used to manipulate neurons in real time? (hint: Ca2+ and light)

1. calcium-sensitive dye: imaging neuron activity in real time; changes in fluorescence intensity are detected using a microscope w/ the objective over the exposed cortical surface; active neuron involves influx of Ca2+ 2. optogenetics: manipulating neurons in real time; genetically encode the light-sensitive protein into the mouse; decide where you want to express it in the brain; affect animal w/ light => manipulate neuron activity in real time! Affect animal behavior

List some cellular and molecular approaches for studying neuron connectivity and identity.

1. injection of radioactive amino acids 2. fluorescent molecules 3. anterograde or retrograde tracers 4. antibody stain 5. RNA probe (in situ hybridization) 6. genetic engineering (ex: encoding a reporter gene such as GFP)

What are the 2 types of NT receptors (NOT voltage-gated)?

1. ionotropic (ligand-gated) 2. metabotropic (GPCR-mediated)

What are the 2 main models of voltage sensing?

1. lateral movement: the voltage sensor is lateral to the pore, and it either pulls up or down on the channel, causing it to either open (depolarization) or close (hyperpolarization) 2. hinging: very similar model as lateral movement model; voltage sensory is like a paddle coming off of the channel, and its movement changes the conformation of the channel; upward movement (toward extracellular side) opens channel and downward movement closes channel *Note: the "movement" of the paddles/voltage sensor portions of the channels is caused by a change in voltage (this is NOT mechanoreception)

What are the three types of membrane potentials?

1. receptor potential: record signal from a receptor, for example, in the fingertip (record from a nerve in that area => recall: nerves = bundles of axons) 2. synaptic potential: stimulate synapse and record signal from soma 3. action potential: record signal traveling down axon

List types of protein channels.

1. voltage-gated 2. ligand-gated 3. mechanoreceptor 4. thermoreceptor Also: active transport (like Na+/K+ pumps, which require ATP)

We started understanding that nerves require stimulation/send electrical signals; start following the paths of nerves and understanding sending and reception of signals; use experimental ablation method to start localizing function; also, development of the idea of phrenology in the (18th/19th/20th) century.

19th century = 1800s

Why are APs unidirectional?

A combination of Na+ channels being inactivated until resting membrane potential is restored and K+ hyperpolarization (ultimately, it's the refractory period!)

Which of the following is NOT an established role for glial cells? A. integrating information to assist neural computation B. maintaining the ionic milieu surrounding nerve cells C. hastening the propagation of neural impulses D. assisting synaptic transmission via NT uptake E. providing scaffolds that assist neural development

A. integrating information to assist neural computation

How will a neuron respond to an injection of negative current? A. it will become hyperpolarized B. it will have a positive electrical response C. it will generate a single action potential D. it will generate multiple action potentials E. it will reach the threshold potential

A. it will become hyperpolarized injection of negative current means negatively charged ions

In an experiment on an animal model in which the synapsin gene is knocked out, you measure the density of synaptic vesicles in the presynaptic terminal within the active zone and outside the active zone in both knockout and control animals. Given what you know about the function of synapsin, what would you expect to find? A. there will be fewer vesicles in the reserve pool in knockout animals than in controls B. there will be more vesicles in the reserve pool in knockout animals than in controls C. there will be no vesicles in the reserve pool in knockout animals than in controls D. there will be no vesicles docked in the active zone in knockout animals E. there will be no difference between knockout animals and controls

A. there will be fewer vesicles in the reserve pool in knockout animals than in controls Recall: synapsin holds vesicles in place, on reserve (Ca2+ dependent protein) synaptotagmin proteins bind to SNARE complex and wait for Ca2+ to bind; once Ca2+ binds, synaptotagmin tightens around SNAREs and causes vesicles to fuse w/ plasma membrane SNARE proteins anchor vesicle to plasma membrane (not Ca2+ dependent)

How would you identify the function of a certain structure?

Ablation (lesion) => trial and error; look for loss of function or change in function; experimental ablation method (still used today...)

afferent v. efferent

Afferent involves the pathway traveling from the periphery to the central nervous system (incoming sensory info) Efferent involves the pathway traveling from the central nervous system to the periphery (outgoing motor info)

If the gene of interest is a mitosis gene and you knock it out, and you don't see a loss of function, what might explain that?

Another gene is compensating; the gene of interest is linked to another gene; redundancy

anterograde v. retrograde tracer

Anterograde tracer: travels from cell body to cell projections; follow axons to the periphery Retrograde tracer: travels from periphery to cell body; who ends here?

antiporter v. symporter

Antiporter: swap ions on the two sides of the membrane (move different ions in opposite directions) Co-transporter (aka symporter): carry multiple ions in the same direction Use the flux of one ion to move another ion; ion exchangers use the electrochemical gradients of co-transported ions as a source of energy

The figure depicts a normal action potential (left) and an action potential altered by application of a toxin (right). What are the source and mechanism of action of the toxin used? *Graphs show in the altered potential, there is prolonged depolarization. A. cone snail; blocks the pore Na+ channels B. scorpion; slows the inactivation of Na+ channels C. scorpion; shifts the voltage dependence of the Na+ channel activation D. wasp; blocks K+ channels E. frog; removes the inactivation and shifts activation of Na+ channels

B. scorpion; slows the inactivation of Na+ channels Prolonged depolarization indicates inhibition of Na+ channels closing.

A researcher conducts a voltage clamp experiment on a giant squid axon and collects the data shown in the graph. At what membrane potential was the cell clamped? *Graph shows only net movement of outward current (line above baseline) A. 0 mV B. sodium's equilibrium potential C. -65 mV D. potassium's equilibrium potential E. -110 mV

B. sodium's equilibrium potential If current is flowing out of the cell, this is probably K+ leaving the cell. If K+ is leaving the cell, this means the cell membrane potential is approaching ENa+, which is about +65 mV. Recall: EKa+ = about -90 mV and ENa+ = +65 mV

How would you prevent your electrode from popping out or breaking when you stimulate a neuron innervating a muscle cell, causing the muscle cell to contract?

Block the post-synaptic receptors so the muscle doesn't contract; find a toxin to do this

How do you test if the inward current is sodium-dependent?

Change [Na+] in cell bath! You could also block Na+ channels (with today's technology) No Na+ in the cell bath will cause Na+ to move OUT of the cell because there's suddenly a driving force to get Na+ out of the cell

channelrhodopsin v. halorhodopsin Both of these proteins are used in what method that allows researchers to manipulate neurons and animal behavior in real time using light?

Channelrhodopsin: light causes it to activate neurons (influx of cations depolarizes cell) Halorhodopsin: light causes it to inhibit neurons (influx of anions hyperpolarizes cell) optogenetics

In the knee-jerk reflex, the afferent neurons A. innervate leg flexor muscles B. innervate leg flexor and extensor muscles C. innervate leg extensor muscles D. are sensory neurons E. are cranial nerves

D. are sensory neurons afferent neurons travel from the PNS to the CNS, carrying sensory info from the periphery

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. it would eliminate the postsynaptic potential and the presynaptic Ca2+ current

The amplitude of the action potential of a given neuron is A. larger in response to depolarizing currents of greater magnitude B. dependent on the magnitude of the sensory stimulus C. related to the number of synapses on the neuron D. smaller if the resting potential of the neuron is lower E. always the same

E. always the same

Subthreshold current injected into an axon flows ____________ along the axon and ____________ with distance from the site of injection. A. actively; remains constant B. actively; decays C. actively; grows D. passively; remains constant E. passively; decays

E. passively; decays SUBthreshold current means it's not enough current to generate an axon potential, so in this case, the depolarization will decay over time

At (EK/ENa), there is no net movement of K+ and only movement of Na+ (into cell) At (EK/ENa), there is no net movement of Na+ and only movement of K+ (out of cell)

EK; ENa

Generally, EPC and EPP will be "opposite" => if current flow is inward, then EPP = depolarization; if current flow is outward, then EPP = hyperpolarization. What is EPC and EPP? *current = flow of cations

EPC = end-plate current EPP = end-plate potential Ex: K+ leaves cell: EPC = outward (outward movement of K+ ions); EPP = hyperpolarization

What is the source of the quanta that make up the EPP? A. pulses of current that flow through the electrical synapse B. fusion of individual synaptic vesicles with the plasma membrane C. individual action potentials D. current through a single ion channel E. short-term increases in membrane permeability

EPP = endplate potential B. fusion of individual synaptic vesicles with the plasma membrane

EPSP and IPSP

EPSP = excitatory post-synaptic potential IPSP = inhibitory post-synaptic potential

Nernst Equation (include variables)

Eion = (RT/zF) ln[ion]o/[ion]i equation that allows you to predict the equilibrium membrane potnetial of a cell if it were permeable to only the single given ion R = gas constant; T = temperature in Kelvin; z = charge of ion; F = Faraday's constant; [ ]o = ion concentration outside the cell; [ ]i = ion concentration inside the cell; ln = natural log

Compare and contrast key features and functions of electrical and chemical synapses.

Electrical synapses involve the direct flow of ions through connexons that form gap junctions, which connect pre-synaptic cells to post-synaptic cells. There are no distinguishing landmarks to differentiate pre- from post-synaptic cells. This type of synapse allows for rapid communication and synchronization of populations of cells (e.g., in the heart). Information travels bidirectionally. Chemical synapses involve a pre- and post-synaptic cell and a synaptic cleft, held together by the extracellular matrix. NT, or signaling molecules, are required for an exchange of information. NTs are released from vesicles on the pre-synaptic side, and NTs bind to receptors on the post-synaptic side (this may be visualized as post-synaptic density). Information travels in one direction, from the pre-synaptic cell to the post-synaptic cell.

If the gene of interest is a mitosis gene and it's successfully knocked out, what do you think a resulting phenotype will be?

Ex: microcephaly => lack of cell growth and underdeveloped parts of the body

True or False: Every neuron has the same length refractory period.

False! Refractory period length varies.

mind-body dualism

Fluid Mechanical Theory couldn't explain everything because humans are more than just moving parts. We're thinking, emotional beings with senses (made in God's image). a. The mind receives sensations and passes it to the brain via the pineal gland b. How do we separate the "mind" from the "brain" (body)? Rene Descartes (1500s)

In the "clam shell" model of the Na+/K+ pump, how many Na+ ions and how many K+ ions are exchanged?

In one cycle, 3 Na+ leave and 2 K+ enter cell The pump undergoes conformational change when switching from being Na+ bound to K+ bound (two different conformations) - but we didn't get into the nitty gritty of this and the different domains of the pump

In voltage clamping, if you gradually increase the membrane potential so it becomes more and more positive, you are moving the cell farther and farther from the equilibrium potential for what ion? This results in (Na+/K+) leaving the cell.

K+; K+ Recall: EK is -58 mV

At rest, neuronal membranes are more permeable to (Na+/K+) than to (Na+/K+). Accordingly, the resting membrane potential is negative and approaches the equilibrium potential for _________.

K+; Na+ K+

(Na+/K+) Channel = 4 separate proteins that come together to create the channel (Na+/K+) Channel = 1 protein folded up to create the channel (encoded by a single gene)

K+; Na+ sodi"um" kinda sounds like "one"...

Spontaneous (EPPs/MEPPs) occur in the absence of presynaptic stimulation.

MEPPs

Pyrethroids is produced by Chrysanthemum flowers, and it is actually used as an insecticide. The toxin prevents closure of (Na+/K+) channels, leaving cells permanently depolarized.

Na+

Sea anemone and cone snails both produce toxins that inhibit (Na+/K+) channel inactivation: calitoxin and delta-conotoxin.

Na+

The scorpion produces bukatoxin, which inhibits (Na+/K+) channel inactivation.

Na+

At resting potential, there is more (Na+/K+) outside the cell and more (Na+/K+) inside the cell due to Na+/K+ pump activity and the fact that when the cell is at rest, Na+ channels are closed (but leak channels are always open).

Na+; K+

During an action potential, the neuron membrane becomes very permeable to (Na+/K+). Thus, the membrane potential becomes positive and approaches the equilibrium potential for __________.

Na+; Na+

Summarize experimental evidence that synaptic vesicles are recycled in the axon terminal.

One study used horseradish peroxidase (HRP) to visualize what happened at the pre-synaptic terminal. The cell's axonal terminal was bathed in HRP, and then later, when extracellular HRP was absent, it was observed that vesicles containing HRP were present in the terminal, showing that the cell had taken up HRP in the synapse and was preparing to use it again.

Why do we recycle NTs?

Plasma membrane needs to maintain its size, so we need a compensatory removal of membrane; also, soma makes proteins and sends them down the axon, so we can't rely on this process every time we need NTs - it's not energy efficient or practical

How would you figure out whether the MEPPs seen in recordings were caused by vesicle release?

Prevent vesicle release and see if the MEPPs are still present. Ex: Block calcium => maybe w/ low [Ca2+] solution or a Ca2+ chelator molecule

Reticular Theory v. Cell Theory (Neuron Doctrine)

Reticular Theory: the body is composed of one continuous network, and signals can travel bidirectionally Cell Theory: the body is composed of discrete cells; the neuron is the fundamental unit of the nervous system

The postsynaptic cell sums (or integrates) all of the EPSPs and IPSPs, resulting in moment-to-moment control of action potential generation. ____________ determines whether or not an action potential occurs

Summation

True or False: CRISPR-Cas9 is a DNA-editing tool that has AMAZING efficiency and success today

True!

"A rise in presynaptic Ca2+ is necessary and sufficient for NT release." Which experimental evidence a) supports the claim that Ca2+ is necessary and b) supports the claim that Ca2+ is sufficient?

a) Ca2+ was shown to be necessary for NT release by blocking Ca2+ channels with a drug/toxin. This resulted in the cell's inability to dock and release vesicles. Also, using a Ca2+ chelator, which absorbs Ca2+, led to the cell's inability to dock and release vesicles. b) Ca2+ was shown to be sufficient for NT release by injecting Ca2+ into the terminal with no action potential, and it was found that the presence of Ca2+ was enough to cause docking and releasing of vesicles. Recall: something is necessary if without it, you can't perform the regular function, and something is sufficient if that something by itself is enough to cause the normal function

If you inject suprathreshold level of current into an axon, you have (active/passive) current flow in the axon, and the amplitude of the potential responses (increases/decreases) as distance from the injection site increases.

active; TRICK QUESTION: suprathreshold current results in an action potential, and we know that the amplitude of the AP is CONSTANT along the length of the axon! There is NO decay of potential over distance, but the onset of the AP is delayed with increasing distance from the injection site.

Hypothesis: If the reversal potential of the ion of interest is not the same as any of the other known reversal potentials for other ions, and it falls between the reversal potential for K+ and Na+, then the channel must be permeable to (either/both) K+ and Na+ ions.

both

Small-molecule NTs are made in the ____________ while neuropeptides are made in the ____________.

bouton (presynaptic terminal); soma

The (greater/smaller) the axon diameter, the (faster/slower) the conductance.

greater; faster

After all these patch clamp experiments looking at Na+ channels and K+ channels, one of the conclusions was: K+ channels take (less time/longer) than Na+ channels to open. __________ acts first, then __________ acts.

longer; Na+; K+

Brevetoxin and Ciguatoxin lower the threshold of activation in neurons, leading to persistent activation and repetitive firing. What can result from this?

lowering threshold increases likelihood of firing => too much activation could lead to epilepsy, for example

MEPPs

miniature end-plate potentials caused by a spontaneous release of vesicles causing mini EPPs; this is not enough depolarization to fire an AP MEPPs let the muscle cell know that the neuron is still there

Voltage-gated Na + channels are present only at the ___________, between stretches of myelin. (Voltage-gated K + channels are present at the nodes of some axons, but not others).

nodes of Ranvier

BTX, produced by the poison dart frog, blocks Na+ channel inactivation. This means that the Na+ channels remain (closed/open), resulting in _____________.

open; Na+ continuing to enter the cell. The cell is never able to return to resting state => over-excitement and potentially seizures

The general rule of postsynaptic action is: If the reversal potential is more (positive/negative) than threshold, excitation results; (excitation/inhibition) occurs if the reversal potential is more negative than threshold.

positive; inhibition

Membrane depolarization rapidly activates a (positive/negative) feedback cycle fueled by the voltage-dependent activation of Na + conductance. This phenomenon is followed by the (faster/slower) activation of a (positive/negative) feedback loop as depolarization activates a K + conductance, which helps to repolarize the membrane potential and terminate the action potential.

positive; slower; negative

Both TTX, produced by ___________, and STX, produced by cyanobacteria, clog the Na+ channel pore, resulting in ____________.

puffer fish; inability to produce action potentials => instant death

The scorpion produces Cll1 toxins, which alter the voltage-dependent opening of Na+ channels and reduce the peak Na+ current. What does this result in?

reducing peak Na+ current may make neurons less likely to fire = not good!

quanta

single vesicle = discrete NT packet that fuses w/ pre-synaptic membrane

active zone (hint: of the presynaptic terminal)

site of synaptic vesicle exocytosis

reversal potential

the membrane potential at which a current switches from moving inward (entering the cell) to moving outward (leaving the cell)

The gates of both Na+ and K+ channels are closed when the membrane potential is hyperpolarized. When the potential is depolarized, ___________ sensors allow the channel gates to open—first the Na + channels and then the K + channels.

voltage Na + channels also inactivate during prolonged depolarization, whereas many types of K + channels do not.