BIOL Review for Class tomorrow (also, remember to do extra practice)

What are nociceptors?

Nociceptors are special sensory neurons that detect painful stimuli (like hard pressure, high heat, or tissue damage). They are activated by such stimuli and transmit information about the stimulus to the spinal cord and then to the brain, where pain is perceived.

What is an axon?

The axon is the long, cable‑like protrusion of a neuron down which the action potential travels. It transmits electrical signals from the cell body to the axon terminals.

In the nociceptor simulation, what direction do action potentials travel?

Action potentials travel toward the brain (from the site of stimulation along the axon toward the spinal cord and then to the brain).

How does a nociceptor communicate with a spinal cord neuron?

When the action potential reaches the end of the nociceptor's axon, it triggers the release of neurotransmitters (chemicals). These neurotransmitters diffuse across the synapse (the gap between neurons) and bind to receptors on the spinal cord neuron, which may generate its own action potential.

In the simulation, when does the spinal cord neuron generate an action potential?

After the nociceptor's action potential reaches the end of the nociceptor. The spinal cord neuron does not fire at the same time; it fires after receiving neurotransmitter from the nociceptor.

What are the main anatomical parts of a typical neuron?

• Cell body (soma) : contains the nucleus.
• Dendrites: tree‑like extensions that receive stimuli or input from other neurons.
• Axon: long cable‑like extension that transmits the action potential.
• Axon terminals: end of the axon where neurotransmitter is released.

What is the receptive field of a sensory neuron?

The receptive field is the specific area (e.g., a region of skin) where a stimulus will activate that neuron. If you strike outside that receptive field, the neuron does not respond, even if its axon passes underneath.

How does the brain figure out where pain is coming from?

The brain determines the location of pain by which nociceptors generate action potentials. Different nociceptors have receptive fields in different specific areas. The brain interprets the pattern of active neurons to localize the stimulus.

What is membrane potential (Vm)?

Membrane potential is a measure of the electrical charge difference across the cell membrane. It reflects how much energy is required to move a single positive charge across the membrane. It is measured in millivolts (mV) . When the inside is negative relative to the outside, Vm is negative.

If the inside of a neuron becomes more positive compared to the outside, what happens to Vm?

Vm increases (becomes more positive). The sign of Vm follows the charge: negative inside = negative Vm; positive inside = positive Vm.

During an action potential, is Vm the same everywhere throughout the neuron?

No. Vm changes as the action potential travels. At any given time, different parts of the axon have different membrane potentials (depolarized where the AP is happening, resting elsewhere).

At the peak of an action potential (highest Vm), is the neuron negatively or positively charged compared to its surroundings?

More positively charged. The inside becomes positive (depolarized), often reaching +30 to +50 mV.

What is the typical resting membrane potential of the neuron in the simulation?

About ‑66 mV. In real neurons, resting Vm is usually between ‑60 and ‑70 mV.

As you move an electrode along the axon, what happens to the timing of the action potential?

The action potential is delayed as you move farther from the stimulation site. It takes time for the AP to travel along the axon (propagation speed is finite).

How does the peak Vm of an action potential change as it travels along the axon?

The peak Vm remains about the same. Action potentials are all‑or‑none and do not decay with distance (they are regenerated along the axon).

Approximately how long does it take an action potential to travel 1 meter in a typical neuron? (From simulation)

About 38 milliseconds for the given neuron length (which represents about 1 meter), giving a speed of roughly 25 m/s. Real speeds range from <1 m/s to nearly 100 m/s.

How does the action potential change as you vary the intensity of the stimulus (from low to high)?

The shape of the action potential does not change. At very low stimulus intensities (below threshold), no action potential occurs. Once threshold is reached, the action potential is identical regardless of stimulus intensity. This is the all‑or‑none property.

What is the threshold stimulus intensity?

The threshold is the minimum stimulus intensity that generates an action potential. Below threshold, no action potential is produced; above threshold, an action potential is always generated.

True or False: Below threshold, an action potential is never generated, so pain sensation is not transmitted from that neuron.

True. If a nociceptor does not reach threshold, it does not fire, and the brain receives no signal from that neuron.

How does a nociceptor indicate the intensity of a painful stimulus?

The intensity is indicated by the number of action potentials (firing rate). A harder hit causes the nociceptor to generate more action potentials (higher frequency), not larger individual APs.

What happens when a motor neuron (motoneuron) fires an action potential?

The motor neuron releases neurotransmitter at its synapse with a muscle fiber. This causes the muscle fiber to produce a brief twitch‑like contraction lasting several milliseconds.

How can a muscle generate a stronger contraction?

The motor neuron generates many action potentials in a brief amount of time (high frequency). If later APs arrive before the muscle has relaxed, the contractions summate (temporal summation), producing a stronger, sustained contraction.

What does botulinum toxin do to motor neurons?

Botulinum toxin prevents the release of neurotransmitter from the motor neuron. As a result, the muscle never contracts, leading to paralysis. (The action potential still travels down the axon, but no neurotransmitter is released.)

In the lidocaine simulation (Part 1), what happens when lidocaine is applied to the middle of the nociceptor?

The action potential stops when it reaches the lidocaine area. It never reaches the axon terminal, so neurotransmitter is not released, and the brain never receives pain information. Lidocaine blocks AP propagation locally.

What is the key property of ion channels regarding ion selectivity?

Ion channels are selective – they allow only certain ions to pass through. For example, K⁺ channels allow K⁺ but not Na⁺, and Na⁺ channels allow Na⁺ but not K⁺.

In the ion movement simulation, which direction can an ion move through its channels?

Both directions (into or out of the cell). Ion channels do not have a built‑in direction; ions move down their electrochemical gradient, which can be inward or outward depending on conditions.

How does Vm change as positively charged ions move across the membrane?

• Vm increases (becomes more positive) when positive charge moves into the cell.
• Vm decreases (becomes more negative) when positive charge moves out of the cell.

What are the two main forces that cause ions to move across a membrane?

1. Diffusion (concentration gradient): ions move from high to low concentration.
2. Electrical force (electrical gradient): opposite charges attract, like charges repel.

In a resting neuron with high K⁺ inside and low K⁺ outside, what happens when K⁺ channels are opened?

More K⁺ moves out of the cell than in (net outward diffusion). This makes the inside more negative (Vm becomes more negative, hyperpolarization).

After K⁺ channels have been open for a few milliseconds, why does net K⁺ movement stop even though the concentration gradient still exists?

As K⁺ leaves, the inside becomes more negative. This negative charge attracts K⁺ back into the cell. Eventually, the electrical force pulling K⁺ in exactly balances the diffusion force pushing K⁺ out, resulting in no net movement. Vm stops changing.

After K⁺ diffuses out, will the cell have a net negative or positive charge compared to its surroundings?

The cell will be negative compared to its surroundings (more negative inside).

As the cell becomes more negative, what happens to K⁺ ions due to electrical forces?

K⁺ ions are attracted to the inside of the cell (opposite charges attract). This inward electrical force opposes further outward diffusion.

In the pool table analogy, what does tipping the table represent?

Tipping the table represents electrical forces. As more balls (ions) move to one side, the table is tipped higher (greater electrical gradient) to balance the random movement (diffusion).

For a positively charged ion (like K⁺ or Na⁺), what happens to its equilibrium potential as the internal concentration increases?

The equilibrium potential becomes more negative. (Because a higher internal concentration drives more outward diffusion, requiring a more negative inside to pull ions back in.)

When both K⁺ and Na⁺ channels are open simultaneously, what is the stable Vm?

The stable Vm is in between the equilibrium potentials of K⁺ and Na⁺. The exact value depends on the relative conductances (permeabilities) of each ion.

If only Na⁺ channels are open (and all others closed), what will Vm become?

Vm will move toward the Na⁺ equilibrium potential (around +50 mV in most neurons). Na⁺ will flow down its gradient until Vm reaches E_Na.

If only K⁺ channels are open, what will Vm become?

Vm will move toward the K⁺ equilibrium potential (around ‑85 to ‑75 mV).

In a typical neuron at rest, Vm is about ‑65 mV. Why is this not equal to the equilibrium potential of any single ion?

Because at rest, multiple ion channels are open (both K⁺ and Na⁺ leak channels). The resting Vm is a weighted average of E_K and E_Na, determined by the relative conductances. K⁺ conductance is higher, so Vm is closer to E_K.

What is conductance in the context of ion channels?

Conductance reflects how easily ions can cross the membrane. It is determined by the number of open channels for a given ion. Higher conductance = more open channels = more ions can move.

As Na⁺ conductance increases (more Na⁺ channels open), what happens to the resting potential?

The resting potential becomes more positive (depolarizes), moving from near E_K toward E_Na. With very high Na⁺ conductance, Vm approaches E_Na.

In a typical neuron at rest, which conductance is larger: Na⁺ or K⁺?

K⁺ conductance is larger. That is why the resting potential is closer to E_K (‑85 mV) than to E_Na (+50 mV).

What is the most negative membrane potential a cell can have (assuming only K⁺ channels open)?

The K⁺ equilibrium potential (typically about ‑85 mV). That is the most negative Vm possible because only K⁺ can move.

What is the most positive membrane potential a cell can have (assuming only Na⁺ channels open)?

The Na⁺ equilibrium potential (typically about +50 mV). That is the most positive Vm possible.

If Na⁺ conductance is suddenly made much larger than K⁺ conductance, what happens to Vm?

Vm will approach the Na⁺ equilibrium potential. The larger the Na⁺ conductance relative to K⁺, the closer Vm gets to E_Na.

What is the role of the Na⁺/K⁺ ion pump?

The Na⁺/K⁺ pump moves K⁺ into the cell and Na⁺ out of the cell, both against their concentration gradients. This restores and maintains the concentration gradients that run down due to leak channels. It requires energy (ATP) and consumes about 20% of our daily food energy.

In the action potential, which conductance increases first?

Na⁺ conductance increases first. The depolarization phase is caused by rapid opening of voltage‑gated Na⁺ channels. K⁺ conductance increases later (delayed).

What are transduction channels?

Transduction channels are ion channels that open or close in response to a specific stimulus (e.g., pressure, heat, light, chemicals). They convert the stimulus into a change in membrane potential (receptor potential).

In the nociceptor, what ion moves through the transduction channel when the hammer strikes?

A positive ion with higher external concentration – specifically Na⁺ (or a non‑specific cation channel). Na⁺ flows into the cell, causing depolarization.

How does the change in Vm on the left side of the neuron differ between a light hammer strike and a hard strike?

With a harder strike, the left side of the neuron reaches a higher maximum Vm (larger depolarization). Stronger stimuli produce larger receptor potentials.

Approximately how high must Vm rise to produce an action potential (threshold)?

About ‑60 to ‑50 mV (from a resting potential of ‑70 mV, that is a depolarization of 10‑20 mV). Exact threshold varies.

What are voltage‑gated ion channels?

Voltage‑gated ion channels are channels that open or close in response to changes in membrane potential. They have a charged gate that is pushed open when Vm becomes sufficiently positive (depolarized). They are essential for action potentials.

How does the initial voltage increase from transduction spread down the axon?

The initial depolarization causes nearby voltage‑gated Na⁺ channels to open. Na⁺ enters, further depolarizing that region, which opens more nearby channels. This creates a chain reaction (regenerative propagation) that travels down the axon.

In the simulation without Na⁺ channel inactivation, why doesn't Vm return to resting potential after Na⁺ channels open?

Because Na⁺ channels remain open, keeping Vm near the Na⁺ equilibrium potential. Without inactivation, Vm stays depolarized.

What is Na⁺ channel inactivation?

Na⁺ channel inactivation is a process where, shortly after opening, voltage‑gated Na⁺ channels transition to an inactivated state where they cannot pass Na⁺ (even if Vm remains depolarized). They must return to resting Vm to recover from inactivation.

What effect does Na⁺ channel inactivation have on the action potential?

Na⁺ channel inactivation allows Vm to fall after the peak (repolarization begins). However, inactivation alone is not sufficient to bring Vm all the way back to resting potential; K⁺ channel opening is also needed.

What is the role of voltage‑gated K⁺ channels in the action potential?

Voltage‑gated K⁺ channels open more slowly than Na⁺ channels in response to depolarization. When they open, K⁺ exits the cell, driving Vm back down toward E_K (repolarization). They do not inactivate; they close when Vm returns to rest.

Why is there no action potential if K⁺ channels open very fast (before Na⁺ channels)?

If K⁺ channels open first, K⁺ leaves the cell, hyperpolarizing or preventing depolarization. Vm moves toward E_K (‑85 mV) instead of toward threshold, so Na⁺ channels never open.

What is the after‑hyperpolarization (AHP) in an action potential?

The after‑hyperpolarization is the phase where Vm drops below the resting potential (more negative) after the action potential. It occurs because K⁺ channels are still open (slow to close) while Na⁺ channels are inactivated, so Vm approaches E_K.

What determines the duration of the after‑hyperpolarization?

The slower K⁺ channels close, the longer the after‑hyperpolarization lasts. While K⁺ channels are open, the cell remains hyperpolarized.

What is the difference between a stimulus below threshold and above threshold in terms of Vm?

Below threshold, Vm never rises high enough to trigger regenerative opening of many Na⁺ channels. Above threshold, enough Na⁺ channels open to cause runaway depolarization (positive feedback), generating an action potential.

What is myelin?

Myelin is a multilayered insulating sheath made of specialized cell membrane (from glial cells) that wraps around the axons of some neurons. It speeds up action potential propagation.

What are Nodes of Ranvier?

Nodes of Ranvier are small gaps in the myelin sheath where the axon membrane is exposed. Voltage‑gated ion channels are concentrated at these nodes. Action potentials "jump" from node to node (saltatory conduction).

How does action potential speed compare between myelinated and unmyelinated neurons of the same length?

The action potential travels faster in the myelinated neuron. Myelin increases propagation speed by allowing saltatory conduction.

Why does the action potential travel faster in myelinated neurons?

In myelinated neurons, the depolarization spreads passively through the insulated internodal region with little decay. When Vm changes at a node, it spreads far enough to reach the next node, where Na⁺ channels open. This "jumping" (saltatory conduction) is much faster than continuous propagation.

What happens to action potential propagation when a region of myelin is damaged (as in multiple sclerosis)?

The action potential may fail to move through the demyelinated region because Vm does not rise high enough to open Na⁺ channels on the far side. Propagation slows or stops.

In the multiple sclerosis simulation, why does the action potential fail after myelin damage?

The demyelinated region has few or no voltage‑gated Na⁺ channels. The passive spread of depolarization through that region decays too much to reach threshold at the next node.

In the crime scene investigation (excess K⁺ injection), what caused the woman's neurons to have a high, unresponsive Vm?

Injection of a large amount of K⁺ (excess extracellular K⁺) raised the K⁺ equilibrium potential (made it less negative). This depolarized all neurons to near E_K (which is now much higher), so they could not respond to stimulation.

Why does excess extracellular K⁺ depolarize neurons?

Increasing extracellular K⁺ reduces the K⁺ concentration gradient. The equilibrium potential for K⁺ becomes less negative (e.g., from ‑85 mV to ‑50 mV). Since resting Vm is dominated by K⁺ conductance, Vm depolarizes toward the new E_K.

In the snake venom investigation, what change reproduced the neuron's abnormal behavior?

Maximum K⁺ conductance is dramatically reduced (K⁺ channels blocked). The venom toxin blocks voltage‑gated K⁺ channels, preventing repolarization and causing prolonged action potentials or seizures.

How does lidocaine work at the molecular level?

Lidocaine blocks voltage‑gated Na⁺ channels, preventing them from opening. This stops action potential generation and propagation, blocking pain signals. You can reproduce this by setting maximum Na⁺ conductance to zero.

What is the all‑or‑none property of action potentials?

Once threshold is reached, an action potential is generated with full amplitude regardless of stimulus intensity. Below threshold, no action potential occurs. Individual action potentials do not vary in size.

How do neurons encode stimulus intensity?

By the frequency (rate) of action potentials and the number of neurons recruited. A stronger stimulus causes a higher firing rate and activates more neurons.

What is saltatory conduction?

Saltatory conduction is the rapid propagation of action potentials in myelinated axons, where the signal "jumps" from one Node of Ranvier to the next. This is much faster than continuous conduction.

What is the relationship between conductance and resistance?

Conductance is the inverse of resistance. Conductance = 1 / Resistance. Higher conductance means more ions flow for a given driving force.

In the Nernst equation, why does the equilibrium potential depend on the log of the concentration ratio?

Because the chemical potential (diffusion force) depends on the logarithm of the concentration ratio, not the absolute difference. This comes from thermodynamics (RT ln([out]/[in])).

If you open both Na⁺ and K⁺ channels and then increase the K⁺ conductance (more K⁺ channels open), what happens to Vm?

Vm becomes more negative (hyperpolarizes), moving closer to E_K because K⁺ conductance now dominates.

Why does capsaicin (chili pepper chemical) cause a burning sensation?

Capsaicin directly opens ion channels (TRPV1 channels) in nociceptors, causing depolarization and generating action potentials even without a painful stimulus. It "tricks" neurons into signaling pain.

What is the difference between transduction channels and voltage‑gated channels?

Transduction channels open in response to physical or chemical stimuli (pressure, heat, light, etc.). Voltage‑gated channels open in response to changes in membrane potential. Transduction channels generate receptor potentials; voltage‑gated channels generate action potentials.

What is the typical equilibrium potential for Na⁺ in a neuron?

About +50 mV (range +40 to +60 mV depending on concentrations).

What is the typical equilibrium potential for K⁺ in a neuron?

About ‑85 mV (range ‑75 to ‑90 mV depending on concentrations).

During the rising phase of an action potential, which ion is moving and in which direction?

Na⁺ moves into the cell (down its electrochemical gradient) through voltage‑gated Na⁺ channels.

During the falling phase (repolarization) of an action potential, which ion is moving and in which direction?

K⁺ moves out of the cell (down its electrochemical gradient) through voltage‑gated K⁺ channels.

Why can't a neuron generate another action potential immediately after one (absolute refractory period)?

Voltage‑gated Na⁺ channels are inactivated and cannot reopen until Vm returns to resting potential and the channels recover. This ensures one‑way propagation and limits firing rate.

What is the relative refractory period?

The period after the absolute refractory period when a stronger‑than‑normal stimulus can generate an action potential. This occurs because the cell is hyperpolarized (after‑hyperpolarization) or some Na⁺ channels are still recovering.

How does myelin increase action potential speed without changing ion channel properties?

Myelin increases the membrane resistance and decreases the capacitance of the insulated regions. This allows the depolarization to spread farther passively, so it can jump to the next node without needing to regenerate along every point.

In the simulation, what happens to Vm when you drag K⁺ ions out of the cell?

Vm becomes more negative (hyperpolarizes) because you are removing positive charge from the inside.

In the simulation, what happens to Vm when you drag Na⁺ ions into the cell?

Vm becomes more positive (depolarizes) because you are adding positive charge to the inside.

What is the definition of equilibrium potential for an ion?

The equilibrium potential is the membrane potential at which the net driving force (electrochemical gradient) for that ion is zero. At that voltage, the electrical gradient exactly opposes the chemical gradient, so there is no net movement of the ion.

If a cell has only K⁺ channels open and Vm is ‑70 mV, but E_K is ‑85 mV, which direction will K⁺ move?

K⁺ will move out of the cell. Vm = ‑70 mV is less negative than E_K = ‑85 mV, so the electrical force pulling K⁺ in is weaker than the chemical force pushing K⁺ out. Net outward movement.

If a cell has only Na⁺ channels open and Vm is ‑70 mV, but E_Na is +50 mV, which direction will Na⁺ move?

Na⁺ will move into the cell. Both the chemical gradient (higher outside) and the electrical gradient (negative inside attracts positive Na⁺) drive Na⁺ inward.

What is the relationship between the number of open channels and conductance?

Conductance is proportional to the number of open channels. More open channels = higher conductance = more ions can cross per unit time for a given driving force.

In the action potential, why does Na⁺ conductance increase rapidly then decrease (inactivate), while K⁺ conductance increases slowly and then decreases slowly?

Voltage‑gated Na⁺ channels have fast activation and fast inactivation (they close after a few ms). Voltage‑gated K⁺ channels have slower activation and no inactivation; they close slowly when Vm repolarizes.

What would happen to the action potential if you removed Na⁺ channel inactivation (channels stayed open)?

The action potential would not repolarize; Vm would stay near E_Na (+50 mV) until the stimulus was removed. The neuron would be stuck depolarized.

What would happen to the action potential if you blocked voltage‑gated K⁺ channels?

Repolarization would be slower or incomplete, resulting in a prolonged action potential (plateau). This can cause excessive neurotransmitter release or seizures.

In the snake venom example, why does blocking K⁺ channels cause muscle seizures?

Blocking K⁺ channels prolongs the action potential, causing more neurotransmitter release at the motor neuron synapse. The muscle receives excessive stimulation, leading to sustained contraction (seizures/spasms).

What is the primary symptom of botulinum toxin poisoning?

Paralysis – muscle weakness and inability to contract, including respiratory muscles, which can be fatal. The toxin prevents neurotransmitter release.

How does lidocaine differ from botulinum toxin in mechanism?

Lidocaine blocks voltage‑gated Na⁺ channels on sensory neurons, preventing action potential generation. Botulinum toxin blocks neurotransmitter release from motor neurons. Both block signal transmission but at different steps.

Why does lidocaine need to be injected near the site of pain (e.g., at the dentist)?

Lidocaine acts locally to block Na⁺ channels on nociceptor axons in that area. If injected elsewhere, it would not reach the relevant nerve fibers. Systemic lidocaine would have widespread effects and potential toxicity.

What is the difference between absolute and relative refractory periods?

Absolute refractory period: no action potential can be generated, regardless of stimulus strength (Na⁺ channels inactivated). Relative refractory period: a stronger‑than‑normal stimulus can generate an action potential (some Na⁺ channels have recovered, but K⁺ channels are still open, making Vm hyperpolarized).