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What is electric potential (voltage)?
The difference in electrical potential per energy per unit charge between two points. Across a neuron’s membrane, it is called the membrane potential (Vm) and is measured in millivolts (mV).
What does a resting potential of -70 mV mean?
The inside of the neuron is 70 mV more negative than the outside. It does not mean the entire inside of the cell is negatively charged; rather, there is a small separation of charge across the membrane.
What is the resting membrane potential (RMP)?
The stable voltage across a neuron’s membrane when it is not generating an action potential. A typical neuron has an RMP near -70 mV, although it varies by cell type.
What is the general distribution of ions across a resting neuron’s membrane?
K+ → Inside → Tends to Diffuse Out
Na+ → Outside → Tends to Diffuse In
Cl- → Usually Outside → Distribution depends on cell type and transporters.
A- (large organic anions, such as proteins) → Inside → generally cannot cross the membrane freely.
what three factors determine the direction and extent of ion movement across a membrane?
1) concentration gradient: ions tend to move from higher to lower concentration.
2) electrical gradient: opposite charges attract; like charges repel.
3) selective permeability: the membrane permits some ions to cross more readily than others, depending on which channels are open.
what is the electrochemical gradient?
the combined influence of the concentration gradient and the electrical gradient of an ion. it determines the ion’s net driving force across the membrane.
in what direction do K+ and Na+ tend to move at rest, and why?
K+: tends to move out because its concentration is higher inside the cell. as positive charge leaves, the inside becomes more negative, electrically pulling K+ back in.
Na+: tends to move in because its concentration is higher outside and the negative interior attracts positive ions.
why doesn’t K+ simply leave the cell until its concentration is equal inside and outside?
because K+ movement creates an electrical gradient. as k+ leaves, the inside becomes more negative, increasingly opposing further K+ efflux. at equilibrium, the electrical force balances the concentration force for that ion.
what is an ion’s equilibrium potential?
the membrane potential at which the electrical gradient exactly balances the concentration gradient for that specific ion, so there is no net movement of that ion through open channels.
individual ions can still move in both directions at equilibrium; the opposing fluxes balance.
what is the difference between an ion’s equilibrium potential and the resting membrane potential?
eq potential: the voltage at which a particular ion is in electrochemical equilibrium.
resting membrane potential: the actual voltage across the membrane, determined by the concentrations and relative permeabilities of multiple ions.
the resting membrane potential is not necessarily equal to any single ion’s equilibrium potnetial.
what does the nernst equation calculate?
the eq potential for a single ion, given its concentration on the two sides of the membrane.
Eion: eq potential of the ion.
R: universal gas constant.
T: temp in Kelvins.
z: ion’s charge (valence), including its sign.
F: Faraday constant, the charge per mole of electrons.
[ion]out: extracellular ion concentration.
[ion]in: intracellular ion concentration.
what happens to an ion’s eq potential if its concentration gradient changes?
its eq potential changes. for example, increasing extracellular K+ generally makes Ek less negative, assuming intracellular K+ stays constant.
if a membrane were permeable only to K+, what would determine its membrane potential?
the k+ concentration gradient and the electrical gradient. the membrane potential would approach Ek, because K+ would be the only permeant ion determining the voltage.
what is the goldman-hodgkin-katz equation used for?
it estimates the membrane potential when multiple ions contribute. it incorporates their concentration gradients and relative membrane permeabilities. unlike the nernst equation, which calculates one ion’s eq potential, the Goldman equation estimates the combined membrane potential.
what is the relative permeability of ions at rest according to my notes?
Pk > Pcl > Pna
potassium has the greatest permeability, chloride is intermediate, and sodium has the lowest of these three in the simplified model.
why is the resting membrane potential close to Ek?
because resting neuronal membrane are generally much more permeable to K+ than to Na+. K+ therefore contributes more strongly to the membrane potential, keeping it relatively negative.
why are organic anions (A-), and how do they influence membrane potential?
they are negatively charged intracellular molecules, including many proteins, that cannot cross the lipid bilayer freely. they help maintain intracellular negative charge, but because they are relatively impermeable, they do not contribute to the membrane potential through direct ion flux in the same way as permeant ions.
how can opening or closing ion channels change the membrane potential?
it changes the membrane’s relative permeability to particular ions. the voltage shifts toward the eq potential of the ion whose permeability increases. for example, opening many Na+ channels increases Na+ permeability, driving the membrane potential toward Ena.
if Ek = -80mV, Ena = +62 mV, and Vm = -71 mV, which way will each ion tend to move through its open channels?
K+ tends to move out of the cell.
Na+ tends to move into the cell.
both movements are consistent with their electrochemical driving forces at this membrane potential.
why is the sodium potassium pump necessary?
because Na+ and K+ continually leak down their electrochemical gradients. the pump maintains their concentration differences, which are essential for the resting membrane potential and repeated neuronal signaling.
how does the sodium potassium pump work?
the Na+/K+-ATPase uses energy from ATP to transport 3Na+ out and 2 K+ in per cycle, against their respective concentration gradients. it is active transport and is electrogenic because it exports one more positive charge than it imports.
does the sodium-potassium pump directly generate the entire resting membrane potential?
no. the resting potential is produced mainly by ion concentration gradients and selective membrane permeability, especially K+ permeability. the pump maintains those gradients and makes a smaller direct contribution to the voltage.
what are ion channels?
transmembrane proteins that form selective pathways through which particular ions can cross the cell membrane down their electrochemical gradients.
what determines an ion channel’s selectivity?
pore size and shape.
the amino acids lining the pore and their chemical properties.
how the channel interacts with the ion’s hydration shell (the water molecules surrounding a dissolved ion).
what is the difference between gated and non-gated ion channels?
non-gated (leak) channels: are generally open and allow ions to move down their electrochemical gradients.
gated channels: open or close in response to a particular signal, such as a change in voltage of the binding of a ligand.
what are examples of non-gated channels, and what do they do?
K+ leak channels help establish the RMP
Some Na+ leak channels also contribute to the resting potential.
K+ channels in glial cells, including astrocytes, help regulate extracellular K+ concentrations.
what is a ligand-gated ion channel?
a channel that opens or closes when a chemical messenger (a ligand) binds to it. at synapses, neurotransmitters often serve as ligands.
what are examples of ligands that can activate ion channels?
neurotransmitters such as glutamate and GABA. depending on the receptor, intracellular Ca2+ or signaling molecules such as cAMP and cGMP can also regulate ion channels.
important distinction: cAMP and cGMP often act through intracellular signaling mechanisms rather than binding directly to the same neurotransmitter-gated channels.
how do ligand-gated channels contribute to synaptic transmission?
a neurotransmitter released from a presynaptic neuron binds to receptors on a target cell, changing channel activity. the resulting ion flow can depolarize or hyperpolarize the postsynaptic membrane.
what is a voltage-gated ion channel?
a channel whose opening and/or closing behavior depends on membrane voltage. a voltage-sending region detects changes in the electrical field across the membrane.
what is the difference between voltage-gated Na+ and K+ channels during an action potential?
voltage-gated Na+ channels generally activate rapidly and then inactivate. voltage-gated K+ channels generally activate more slowly and help repolarize the membrane.
do voltage-gated channels only respond to voltage when opening?
no. voltage can affect both activation and deactivation, as well as inactivation in channels that have this property. the important exam concept is that channel state transitions are voltage-dependent; they are not all governed by one identical opening mechanism.
what are the three major states of a typical voltage-gated Na+ channel?
Resting: closed but available; the channel can open if the membrane depolarizes sufficiently.
Open: activated; depolarization rapidly opens the activation gate, allowing Na+ to flow into the neuron.
Inactivated: closed and temporarily unavailable; the inactivation gate closes. the channel cannot reopen immediately, even if the membrane remains depolarized.
how does a voltage-gated Na+ channel return to its resting state?
repolarization allows the inactivation gate to reopen and the activation gate to close. the channel becomes closed but available for another action potential.
activation gate - voltage sensitive part of voltage channel that opens in response to depolarization
why is na+ channel inactivation important?
it stops the rapid Na+ influx that drives depolarization and contributes to the absolute refractory period, helping ensure that action potentials are discrete events.
what is depolarization?
a change in membrane potential toward a more positive value. for example, a change from -70 mV to -55mV is depolarization.
what is hyperpolarization?
a change in membrane potential toward a more negative value. for example, a change from -70 mV to -80 mV is hyperpolarization.
what is repolarization?
the return of the membrane potential toward its resting value after depolarization, primarily due to Na+ channel inactivation and K+ efflux during a typical neuronal action potential.
what is the threshold of excitation?
the membrane potential at which sufficient voltage-gated Na+ channels activate to initiate a self-regenerating action potential. a typical value is approx -50 to -55 mV, although it varies by neurons.
why does reaching threshold cause a rapid, self-amplifying depolarization?
depolarization opens voltage-gated Na+ channels. Na+ enters, making the membrane more positive and opening additional Na+ channels. this is a positive feedback loop.
what is an action potential?
a rapid, temporary reversal of a neuron’s membrane potential produced by the coordinated opening and closing of voltage-gated ion channels. it allows electrical signals to travel along the axon.
what does ‘all or none’ mean?
if a stimulus brings the membrane to threshold, an action potential is generated with a characteristic amplitude. a stimulus that does not reach threshold does not generate a full action potential.
stronger stimuli do not make an individual action potential larger.
what happens when a stimulus is below threshold?
it produces a graded potential: a local change in membrane voltage whose amplitude depends on stimulus strength. it may dissipate before reaching the trigger zone and does not necessarily produce an action potential.
what are the properties of graded potentials vs action potentials?
graded:
amplitude: varies with stimulus strength
threshold: not required to generate the local change.
propagation: decreases with distance.
summation: can summate
main role: integrates incoming signals.
action:
amplitude: relatively constant.
threshold: required for initiation.
propagation: regenerated without decrement.
summation: individual action potentials do not summate in amplitude.
main role: carries signals along the axon.
what is decremental conduction?
the reduction in the amplitude of a passive electrical signal as it spreads away from its source. this is a characteristic of graded potentials and passive spread under myelin.
what is the rate law?
the strength of a sustained stimulus is represented by the frequency of action potentials, rather than the amplitude of each action potential. a stronger stimulus generally produces a higher firing rate, up to the neuron’s limits.
if a stimulus is twice as strong, will the action potential amplitude double?
no. the amplitude of an individual action potential remains relatively constant. a stronger stimulus may increase the firing frequently or recruit more neurons.
does having more Na+ channels mean that a neuron automatically fires more action potentials?
no. the number and properties of available Na+ channels influence excitability and the action potential’s characteristics, but firing rate is also dependent on the stimulus, threshold, other channels, and refractory periods.
*what are the main phases of a typical neuronal action potential?
resting potential: the membrane is near -70mV. most voltage-gated Na+ and K+ channels are closed, while leak channels remain active.
threshold and depolarization: threshold is reached; voltage-gated Na+ channels open rapidly, and Na+ enters the cell.
peak (overshoot): the membrane potential becomes positive. Na+ channels inactivate, while voltage-gated K+ channels are increasingly open.
repolarization: K+ leaves the cell through open voltage-gated K+ channels, bringing the membrane potential back toward negative values.
undershoot (after hyperpolarization): K+ channels remain open briefly, so the membrane potential becomes more negative than the resting potential.
return to rest: voltage-gated K+ channels close, Na+ channels recover from inactivation, and leak currents plus ion transporters maintain the resting conditions.
why does the peak of an action potential become positive?
Na+ permeability rises sharply as voltage-gated Na+ channels open, driving the membrane potential toward the positive Na+ eq potential. the peak usually does not reach ENa, because Na+ channels inactivate and K+ permeability increases.
what causes repolarization?
primarily, Na+ channel inactivation reduces inward Na+ current while the delayed opening of voltage-gated K+ channels increases outward K+ current.
what causes the undershoot?
voltage-gated K+ channels close relatively slowly. K+ continues leaving the cell after the membrane has returned to its resting voltage, temporarily making the inside more negative than at rest.
what is difference between overshoot and undershoot?
overshoot: the portion of the action potential above 0 mV.
undershoot: the after hyperpolarization below the resting membrane potential.
does the sodium potassium pump restore the membrane potential after ever action potential?
not by itself, and not on the rapid timescale of an individual action potential. the immediate voltage changes mainly result from ion currents through channels. the pump maintains and gradually restores the Na+ and K+ concentration gradients over time.
why do voltage-gated Na+ channels open and inactivate faster than voltage-gated K+ channels activate?
their gating mechanisms have different kinetics. rapid na+ channel activation produces the rising phase, while slower K+ channel activation produces much of the falling phase and undershoot.
what is the refractory period?
the period during and after an action potential when a neuron cannot generate another action potential normally, or requires a stronger stimulus than usual.
what is the absolute refractory period?
the period when a second action potential cannot be generated, regardless of stimulus strength, because too many voltage-gated Na+ channels are inactivated.
what is the relative refractory period?
the period when a second action potential is possible, but a stronger-than-usual stimulus is required. some Na+ channels have recovered, but elevated K+ conductance and the undershoot make threshold harder to reach.
why can an action potential sometimes occur during the undershoot?
during the relative refractory period, a sufficiently strong stimulus can depolarize the membrane to threshold even through the membrane is hyperpolarized. the neuron does not always have to return fully to its resting potential before firing again.
how do the absolute and relative refractory periods differ in terms of Na+ channels?
absolute: many Na+ channels are inactivated and unavailable.
relative: more Na+ channels have recovered, but the membrane is less excitable than usual, often becomes K+ conductance remains elevated.
how do refractory period help action potential travel in one direction?
the membrane region immediately behind the advancing action potential is refractory. it is therefore less able to fire again immediately, favoring forward propagation, rather than backward re-excitation.
what is propagation of an action potential?
the transmission of an action potential along an axon. local currents from an active region depolarize the adjacent membrane, bringing it to threshold and regenerating the action potential.
what is continuous conduction?
the step by step regeneration of an action potential along an unmyelinated axon. each adjacent segment of membrane must be depolarized and activated.
what is myelin?
a lipid and protein rich insulating sheath surrounding many axons. in the CNS, it is produced by oligodendrocytes; in the PNS it is produced by Schwann cells.
is myelin found only in vertebrates?
no - myelin is a characteristic of vertebrate nervous systems, but the key exam distinction is that not all vertebrate axons are myelinated (some are unmyelinated).
why can’t ions freely cross the membrane beneath a myelin sheath?
myelin increases membrane resistance and decreases membrane capacitance, reducing current leakage across the insulated regions. it does not mean that ions are physically unable to cross the underlying membrane; rather, ion movement across those regions is greatly reduced, and voltage-gated channels are concentrated at the nodes of Ranvier.
action potentials regenerated at nodes
what are the nodes of ranvier?
small gaps between adjacent myelin segments where the axonal membrane is exposed and contains a high density of voltage-gated Na+ channels. these are the main sites where action potentials are regenerated in myelinated axons.
what is saltatory conduction?
the propagation of an action potential from one node of Ranvier to the next in a myelinated axon. electrical current spreads rapidly beneath the myelin, depolarizing the next node, where the action potential is regenerated.
why is saltatory conduction faster than continuous conduction?
myelin reduces current leakage and lowers the membrane capacitance, so the next node can be depolarized more quickly. the action potential is regenerated at the nodes rather than along every point of the axonal membrane.
why is salt. conduction more energy efficient?
much less membrane area undergoes large Na+ and K+ fluxes during each action potential. consequently, fewer ions need to be transported back against their gradients, reducing the ATP needed by the Na+/K+ pump.
does the action potential literally jump over the myelin sheath?
not exactly. the local electrical current spreads passively beneath the myelin. the action potential is regenerated at each node of Ranvier, giving the apperance that it jumps from node to node.
what is the difference between passive current spread and action potential propagation?
passive current spread: voltage changes spread along the membrane and decrease with distance.
action potential propagation: passive current brings the next region to threshold, and voltage-gated channels regenerate the full action potential there.
what would happen if myelin were damaged?
current leakage would increase, and conduction could slow or fail. this can disrupt communication between neurons and is one reason demyelinating disorders can cause neurological symptoms.
a neuron is at -70 mv. many na+ channels open. what happens and why?
na+ enters the neuron down its electrochemical gradient. the inside becomes more positive, causing depolarization toward ENa.
a neuron is at -70mV. many K+ channels open. what happens?
k+ generally exits the neuron because its eq potential is more negative than -70mV. the inside becomes more negative, producing hyperpolarization toward Ek.
a neuron is depolarization from -70 mV to -60 mV, but threshold is -50mV. has action potential occurred?
no - this is subthreshold depolarization (may be a graded potential).
what happens if the membrane becomes more permeable to na+ than to K+?
the membrane potential shifts toward Ena, producing depolarization. if threshold is reached, an action potential can begin.
Why does a stronger stimulus generally produce a higher action potential firing rate instead of a larger action potential?
Individual action potentials are all-or-none events with relatively constant amplitude. A stronger sustained stimulus generally causes the neuron to reach threshold more frequently, increasing firing frequency.
Why does an action potential not normally weaken as it travels along an axon?
It is actively regenerated by voltage-gated channels in successive regions of the membrane. Each region produces a new action potential rather than relying entirely on passive current spread.
A drug blocks voltage-gated Na⁺ channels. What effect would you expect?
It would reduce or prevent the rapid depolarization needed to initiate and propagate action potentials. The exact effect depends on which channels are blocked and how extensively they are inhibited.
A drug blocks voltage-gated K⁺ channels. What effect would you expect?
Repolarization would generally become slower, and the undershoot might be reduced or altered. The exact effect depends on which K⁺ channel types are blocked.
What happens if the Na⁺/K⁺ pump stops working for an extended period?
Na⁺ and K⁺ concentration gradients gradually deteriorate because ions continue moving through channels without being adequately transported back. The resting membrane potential and the ability to generate repeated action potentials would eventually be disrupted.
Why does opening a channel not always depolarize the membrane?
The effect depends on which ion passes through the channel and the direction of its electrochemical driving force. Na⁺ influx usually depolarizes, K⁺ efflux usually hyperpolarizes or repolarizes, and Cl⁻ movement depends on its equilibrium potential relative to the membrane potential.
Why is the resting membrane potential closer to Ek than to ENa
Because the resting membrane is much more permeable to K⁺ than to Na⁺. The Goldman equation accounts for this difference in permeability.
How do ion channels and the sodium–potassium pump work together?
Ion channels permit rapid, passive ion movement that changes the membrane potential. The Na⁺/K⁺ pump uses ATP to maintain the concentration gradients that make this signaling possible.
unmyelinated vs myelinated axon.
unmyelinated:
conduction: continuous
regeneration: along successive membrane segments.
speed: slower
energy used: higher
myelinated:
saltatory:
regeneration: at nodes of ranv.
speed: faster
energy used: lower
how can voltage-gated sodium channels be used to manipulate neuronal activity?
blocking voltage-gated Na+ channels prevents the inward sodium current required for action potential initiation and propagation. this can stop neurons from transmitting signals.
how does lidocaine work as a local anesthetic?
lidocaine blocks voltage gated Na+ channels in nerves, preventing action potentials from propagating and temporarily eliminating sensation in the affected area. (same as TTX - neurotoxin in pufferfish)
how does tetrodotoxin (TTX), a pufferfish neurotoxin, affect neurons?
TTX blocks voltage-gated Na+ channels, preventing action potentials, and potentially causing paralysis.
what is artifical electrical stimulation of the brain?
applying electrical current through an electrode to activate neurons in a specific brain region. researchers can then observe the resulting behavior or physiological response to infer the region’s function.
what is the lateral hypothalamus involved in?
it contributes to motivated behaviors, including eating, drinking, and reward-related processes.
what is optogenetics?
a technique that uses light-sensitive proteins called opsins to control neuronal activity with high spatial and temporal precision.
where did the light-sensitive proteins used in optogenetics originate?
some opsins, including channelrhodopsins, were discovered in algae and adapted for use in neurons.
how does channelrhodopsin activate a neuron?
blue light opens channelrhodopsin channels, allowing positively charged ions, especially Na+, to enter. this depolarizes the membrane and can trigger an action potential.
how can optogenetics inhibit neuronal activity?
researchers can express inhibitory opsins that respond to particular wavelengths of light by hyperpolarizing neurons or otherwise reducing their excitability.
why is optogenetics useful for neuroscience research
it allows researchers to activate or inhibit selected neurons and determine how their activity contributes to behavior or brain function.
what is a presynaptic neuron?
the neuron that sends a signal to another cell by releasing neurotransmitters at a chemical synapse or transmitting current at an electrical synapse.
what is a postsynaptic neuron?
the neuron that receives the signal from the presynaptic neuron.
what do afferent and efferent mean when describing a synapse between two neurons?
afferent refers to the signal arriving at the neuron or structure being considered; efferent refers to the signal leaving it. these terms depend on the reference point.
what is an afferent axon or projection relative to a brain region?
an axon that carries information into that brain region.