18). Q&A: Action Potential and Signal Propagation

80 Question and Answer flashcards covering Action Potential and Signal Propagation from OPT8101 - Biomedical Sciences I.

What is the title and course code of the lecture taught by Dr. Joshua Scheys?

OPT8101 - Biomedical Sciences I: Action Potential and Signal Propagation.

In cellular physiology, how is "excitability" defined?

The ability of a cell to rapidly alter its membrane permeability to selective ions upon adequate stimulation, thereby changing its membrane potential ($V_m$).

Which two primary cell types possess the property of excitability?

Neurons and muscle cells.

What is the extracellular fluid (ECF) concentration of $\text{Na}^+$ ions?

$$142\,\text{mM}$$

What is the intracellular fluid (ICF) concentration of $\text{Na}^+$ ions?

$$10\,\text{mM}$$

What is the extracellular fluid (ECF) concentration of $\text{K}^+$ ions?

$$4\,\text{mM}$$

What is the intracellular fluid (ICF) concentration of $\text{K}^+$ ions?

$$140\,\text{mM}$$

What is the extracellular fluid (ECF) concentration of $\text{Ca}^{2+}$ ions?

$$2.4\,\text{mM}$$

What is the intracellular fluid (ICF) concentration of $\text{Ca}^{2+}$ ions?

$$0.0001\,\text{mM}$$

What is the extracellular fluid (ECF) concentration of $\text{Cl}^-$ ions?

$$105\,\text{mM}$$

What is the intracellular fluid (ICF) concentration of $\text{Cl}^-$ ions?

$$4\,\text{mM}$$

According to the lecture notes, what effect does the movement of ions through open channels have on a cell?

It causes a change in voltage across the membrane.

What are the four general methods of ion channel activation shown on Slide 5?

Voltage-gated, ligand-gated (extracellular ligand), ligand-gated (intracellular ligand), and mechanically gated.

When do voltage-gated ion channels open?

When the membrane potential reaches a threshold value.

How is a "stimulus" defined in the context of membrane excitability?

Something that elicits a local change in ion channel permeability.

What is a graded potential?

A change in membrane potential caused by a change in current.

What types of stimuli can induce graded potentials?

Molecule binding to a receptor (neurotransmitter, hormone, paracrine factor) and sensory stimuli (touch, pressure, light, sound, temperature).

What factor determines the amplitude of a graded potential?

Stimulus strength.

What factor determines the direction (depolarization vs. hyperpolarization) of a graded potential?

The specific type of ion passing through the opened channels.

How does Ohm's Law ($V = IR$) apply to graded potentials?

A change in current ($I$) produces a proportional change in membrane potential ($V$).

What is meant by "decremental conduction" in graded potentials?

The charge dissipates as it travels farther from the initial site of depolarization, so the stimulus only affects the membrane locally.

What two properties of a graded potential are determined by the intensity of the initial stimulus?

The magnitude of the change in membrane potential and the distance along the membrane that the stimulus will affect.

What are two mechanisms by which threshold is reached to open voltage-gated channels?

Opening of ligand-gated channels (e.g., neurotransmitter receptor channels) and local current flow from an action potential in a neighboring region.

What is the "all-or-none" principle of an action potential?

If threshold is reached, an action potential fires completely with an identical amplitude every time; if threshold is not reached, no action potential fires.

Besides neurons and muscle cells, what other cell types are capable of producing action potentials?

Certain endocrine, immune, and reproductive cells.

Where along a neuron is there a high expression of voltage-gated ion channels?

Along axons.

How do the opening speeds of voltage-gated $\text{Na}^+$ and $\text{K}^+$ channels compare upon depolarization?

Voltage-gated $\text{Na}^+$ channels open very rapidly, whereas voltage-gated $\text{K}^+$ channels open more slowly.

What are the three transition states of a voltage-gated $\text{Na}^+$ channel?

Closed, Open, and Inactivated.

Where is the inactivation gate located on a voltage-gated $\text{Na}^+$ channel, and what does it do?

It is located on the cytoplasmic side of the channel and blocks the flow of ions shortly after the channel opens.

What condition must be met before an inactivated voltage-gated $\text{Na}^+$ channel can open again?

The channel must first return to the closed state, which occurs when $V_m$ reaches resting membrane potential.

What occurs during Phase 1 and Phase 2 of an action potential?

Phase 1 is Resting Membrane Potential; Phase 2 occurs when a depolarizing stimulus causes the membrane to reach threshold, opening voltage-gated $\text{Na}^+$ channels.

What occurs during Phase 3 (rapid depolarization or rising phase) of an action potential?

Opening of additional voltage-gated $\text{Na}^+$ channels causes a rapid influx of $\text{Na}^+$ into the cell.

What two events define Phase 4 (Peak) of an action potential?

Voltage-gated $\text{Na}^+$ channels are inactivated AND voltage-gated $\text{K}^+$ channels open.

What ionic movement drives Phase 5 (repolarization) of an action potential?

Efflux of $\text{K}^+$ out of the cell.

What occurs during Phase 6 and Phase 7 of an action potential?

Phase 6 is hyperpolarization; Phase 7 is recovery to resting $V_m$, where both $\text{Na}^+$ and $\text{K}^+$ channels are closed.

How does permeability change during an action potential compare between $\text{Na}^+$ and $\text{K}^+$ channels?

There is a much greater change in permeability when voltage-gated $\text{Na}^+$ channels open than when voltage-gated $\text{K}^+$ channels open.

What compound blocks $\text{K}^+$ current, revealing only the $\text{Na}^+$ inward current?

TEA (tetraethylammonium).

What two toxins block $\text{Na}^+$ current, revealing only the $\text{K}^+$ outward current?

TTX (tetrodotoxin) and STX (saxitoxin).

What are the biological sources of TTX and STX?

TTX is from pufferfish; STX is from "red tide" dinoflagellates.

What happens to the shape of an action potential peak if a cell also expresses voltage-gated $\text{Ca}^{2+}$ channels that do not rapidly inactivate?

It develops a broad peak.

Which cell type is given as an example of having a broad-peak action potential due to $\text{Ca}^{2+}$ channels?

Atrial muscle cells.

What is the definition of the absolute refractory period?

The period during which a second response is not possible, regardless of the strength or duration of the stimulus.

What is the molecular mechanism behind the absolute refractory period?

Voltage-gated $\text{Na}^+$ channels are inactivated and cannot reopen.

What is the definition of the relative refractory period?

The period during which a second response can be elicited, but requires a stronger stimulus.

What state of the membrane causes the requirement for a stronger stimulus during the relative refractory period?

The membrane is hyperpolarized.

What functional role does the refractory period play in action potential propagation along axons?

It limits action potential frequency and ensures one-way travel along neurons.

Why does an action potential maintain a constant magnitude down an axon while a graded potential decays?

An action potential is constantly "recharged" because of the activation of neighboring voltage-gated $\text{Na}^+$ channels.

Compare the directionality options of graded potentials versus action potentials.

Graded potentials can be depolarizing or hyperpolarizing, whereas action potentials are only depolarizing during their initial event.

What three factors affect the speed of signal propagation in neurons?

Axon diameter (ICF volume), myelination (insulator), and expression of voltage-gated ion channels.

Why does a larger axon diameter result in faster action potential propagation?

Larger diameter means more intracellular fluid volume, which provides less resistance to local current flow.

How does myelin increase conduction speed?

It insulates the axon and prevents leakage of charge.

What feature of the Nodes of Ranvier enables rapid spike propagation?

They have a very high density of voltage-gated $\text{Na}^+$ channels.

A myelinated axon of $\text{10}\,\mu\text{m}$ diameter is equivalent in conduction speed to an unmyelinated axon of what diameter?

$$500\,\mu\text{m}$$

What is saltatory conduction?

The process in which action potentials appear to "jump" from one node to the next as they propagate along a myelinated axon.

Compare the propagation speed and head-to-toe travel time of unmyelinated versus myelinated axons.

Unmyelinated: $0.5\,\text{m/s}$ ($4\,\text{seconds}$ head to toe); Myelinated: $100\,\text{m/s}$ ($0.02\,\text{seconds}$ head to toe).

What are the function, diameter, myelination, and speed of Type A $\alpha$ peripheral fibers?

Function: Somatomotor, proprioception; Diameter: $12\text{--}20\,\mu\text{m}$; Myelin: Yes; Speed: $80\text{--}120\,\text{m/s}$.

What are the function, diameter, myelination, and speed of Type A $\beta$ peripheral fibers?

Function: Touch, pressure; Diameter: $5\text{--}12\,\mu\text{m}$; Myelin: Yes; Speed: $35\text{--}75\,\text{m/s}$.

What are the function, diameter, myelination, and speed of Type A $\gamma$ peripheral fibers?

Function: Motor to muscle spindle; Diameter: $3\text{--}6\,\mu\text{m}$; Myelin: Yes; Speed: $12\text{--}30\,\text{m/s}$.

What are the function, diameter, myelination, and speed of Type A $\delta$ peripheral fibers?

Function: Acute pain/temp, fine touch; Diameter: $2\text{--}5\,\mu\text{m}$; Myelin: Yes; Speed: $5\text{--}30\,\text{m/s}$.

What are the function, diameter, myelination, and speed of Type B peripheral fibers?

Function: Preganglionic autonomic; Diameter: $<3\,\mu\text{m}$; Myelin: Yes; Speed: $3\text{--}15\,\text{m/s}$.

What are the function, diameter, myelination, and speed of Type C peripheral fibers?

Function: Aching pain, touch (sensory) or postganglionic autonomic; Diameter: $0.3\text{--}1.3\,\mu\text{m}$; Myelin: No; Speed: $0.5\text{--}2.5\,\text{m/s}$.

What five effects occur as a result of demyelination along an axon?

1. Decreased conduction velocity, 2. Frequency-related block, 3. Total conduction block, 4. Ectopic impulse generation, and 5. Increase in mechanosensitivity.

What is "crosstalk" in demyelinated axons, and in what direction does the action potential propagate in the adjacent neuron?

Leakage of charge from one demyelinated neuron activates an action potential in a neighboring neuron; it propagates in both directions from the demyelination site.

What are the pathology, target cell, and recovery potential of Multiple Sclerosis (MS)?

MS is an autoimmune disease of the CNS that destroys oligodendrocytes; recovery is minimal.

What are the pathology, target cell, and recovery potential of Guillain-Barré syndrome?

Guillain-Barré is a PNS condition involving lymphocytic infiltration of Schwann cells following viral infection; recovery occurs when remyelinated.

What spiking pattern occurs if an inhibitory interneuron remains depolarized above threshold?

Continuous, high-frequency trains of action potentials.

How do spiking patterns differ between small pyramidal cells and large pyramidal cells upon sustained depolarization?

Small pyramidal cells exhibit an adapting (slowing) firing pattern, whereas large pyramidal cells fire in repetitive bursts.

Are bulk ICF and ECF ion concentrations appreciably changed by a single action potential?

No, ion concentrations in ICF and ECF are not appreciably changed by an action potential.

How many $\text{Na}^+$ ions cross the membrane during a $2\,\text{msec}$ action potential to change $V_m$ by $100\,\text{mV}$, and what percentage of internal $\text{Na}^+$ is this?

Approximately $40\text{ million}$ ($40 \times 10^6$) $\text{Na}^+$ ions cross, representing only $0.06\%$ of the $\text{Na}^+$ inside the cell.

What clinical consequences result from ingesting Tetrodotoxin (TTX)?

Loss of action potential propagation, leading to numbness, loss of feeling, paralysis, and loss of control over respiratory muscles.

What happens if voltage-gated $\text{Na}^+$ channels are prevented from closing/inactivating?

No action potentials can fire because channels are stuck in the absolute refractory period.

What is the molecular target and mechanism of action of local anesthetics (LA)?

LA binds to the cytoplasmic side of voltage-gated $\text{Na}^+$ channels and interacts with the inactivation gate to maintain the channel in the inactive state.

What is the chemical equilibrium formula for local anesthetics in solution?

$$\text{RNH}^+ \rightleftharpoons \text{RN} + \text{H}^+$$

In local anesthetic chemistry, which form is the uncharged free base ($\text{RN}$) and what is its role?

$\text{RN}$ is the free base form that is able to cross the nerve sheath and cell membrane.

In local anesthetic chemistry, which form is the ionized salt ($\text{RNH}^+$) and what is its role?

$\text{RNH}^+$ is the active ionized form that plugs the channel from the cytoplasmic side.

How does a decrease in tissue pH affect the equilibrium $\text{RNH}^+ \rightleftharpoons \text{RN} + \text{H}^+$?

It shifts the equilibrium to the left, increasing the ionized form ($\text{RNH}^+$) and decreasing the free base form ($\text{RN}$).

Why is the effectiveness of local anesthetics reduced in infected or inflamed tissue?

Infection/inflammation lowers tissue pH, which shifts LA to the ionized form ($\text{RNH}^+$) and leaves less free base ($\text{RN}$) available to cross the membrane.

How do vasoconstrictors included in local anesthetic solutions affect solution pH?

Vasoconstrictors tend to lower the pH of the solution.

By how much is local anesthetic effectiveness reduced when tissue pH drops from $7.4$ to $6$?

Effectiveness is reduced by over $20\text{-fold}$.

In Slide 40's example, out of $1000$ injected LA molecules, how many active intracellular $\text{RNH}^+$ molecules are formed at pH $7.4$ versus pH $6$?

At pH $7.4$, $180$ active intracellular $\text{RNH}^+$ molecules are formed; at pH $6$, only $7.5$ active intracellular $\text{RNH}^+$ molecules are formed.