Electrical Signaling in Neurons (4C) - Chem & Physics

1. During the rising phase of an action potential, which voltage-gated channel opens first?

   Voltage-gated $\text{Na}^+$ channels. These channels activate at threshold, allowing rapid sodium influx that drives the membrane potential toward the sodium equilibrium potential.

2. If extracellular $\text{K}^+$ rises (hyperkalemia), what is the immediate effect on resting $V_m$?

   Resting $V_m$ depolarizes (becomes less negative). Elevated extracellular potassium shifts the potassium equilibrium potential less negative, pulling the resting potential toward it via leak channels.

3. Which ions have the highest extracellular concentrations in typical neurons: $\text{Na}^+$ or $\text{K}^+$?

   $\text{Na}^+$ has the higher extracellular concentration. Sodium ions are actively pumped out of the neuron by the Na+/K+ ATPase, establishing a higher concentration in the extracellular fluid compared to potassium.

4. Which direction does $\text{K}^+$ move through open channels at rest: into or out of the neuron?

   Out of the neuron (down its concentration gradient). At resting potential, the concentration gradient drives potassium efflux, outweighing the opposing electrical gradient.

5. What is hyperpolarization of a neuron in terms of membrane potential $V_m$?

   $V_m$ becomes more negative than resting potential. Hyperpolarization results from increased potassium efflux or chloride influx, enhancing the negative charge inside the neuron.

6. What is the approximate Nernst equation at $37^\circ\text{C}$ using base-10 logs?

   $E\approx\frac{61\ \text{mV}}{z}\log\left(\frac{[\text{out}]}{[\text{in}]}\right)$. At body temperature, the Nernst equation simplifies to this form for easier computation using base-10 logarithms and millivolt units.

7. What is saltatory conduction?

   Apparent "jumping" of depolarization between nodes in myelinated axons. Myelin prevents ion flux between nodes, allowing passive current spread that depolarizes the next node, speeding conduction.

8. Which change increases action potential conduction velocity more: increased myelination or decreased myelination?

   Increased myelination. Myelination insulates the axon, reducing capacitance and enabling faster saltatory conduction between nodes of Ranvier.

9. If $[\text{Na}^+]_\text{out}$ decreases while $[\text{Na}^+]_\text{in}$ is constant, what happens to $E_{Na}$?

   $E_{Na}$ becomes less positive (moves toward $0$). Decreasing extracellular sodium reduces the concentration gradient, making the equilibrium potential less positive per the Nernst equation.

10. What is the typical sign of the resting membrane potential $V_m$ relative to the outside of the cell?

    Negative inside relative to outside (typically about $-70\ \text{mV}$). The resting membrane potential is negative due to the dominance of potassium leak channels and the electrochemical gradients maintained by ion pumps.

11. What is the relative refractory period primarily due to in an action potential?

    Persistently open $\text{K}^+$ channels and hyperpolarization. Delayed closure of potassium channels causes afterhyperpolarization, raising the threshold for subsequent action potentials.

12. If $[\text{K}^+]_\text{out}$ increases while $[\text{K}^+]_\text{in}$ is constant, what happens to $E_K$?

    $E_K$ becomes less negative (moves toward $0$). Increasing extracellular potassium reduces the concentration gradient, shifting the equilibrium potential toward zero according to the Nernst equation.

13. What type of ion channel primarily sets the resting membrane potential in many neurons?

    $\text{K}^+$ leak channels. Potassium leak channels allow greater passive flux of K+ than other ions at rest, driving the membrane potential close to the potassium equilibrium potential.

14. Which ions have the highest intracellular concentrations in typical neurons: $\text{Na}^+$ or $\text{K}^+$?

    $\text{K}^+$ has the higher intracellular concentration. Potassium ions are actively pumped into the neuron by the Na+/K+ ATPase, resulting in a higher intracellular concentration than sodium.

15. In myelinated axons, at which structures are action potentials regenerated?

    Nodes of Ranvier. These unmyelinated gaps concentrate voltage-gated channels, allowing regeneration of the action potential and efficient propagation.

16. What causes the falling phase (repolarization) of the neuronal action potential?

    $\text{Na}^+$ channel inactivation plus opening of voltage-gated $\text{K}^+$ channels. Sodium channel inactivation halts influx, while potassium channel opening promotes efflux, restoring the membrane potential to resting levels.

17. What is depolarization of a neuron in terms of membrane potential $V_m$?

    $V_m$ becomes less negative (moves toward $0$ or positive). Depolarization occurs when positive ion influx or negative ion efflux reduces the magnitude of the negative membrane potential.

18. Which direction does $\text{Na}^+$ move through open channels at rest: into or out of the neuron?

    Into the neuron (down its electrochemical gradient). At resting potential, the electrochemical gradient favors sodium influx due to both concentration and electrical driving forces.

19. Identify the property that makes action potentials non-decremental along the axon.

    Regenerative opening of voltage-gated channels along the membrane. Local depolarization triggers sequential activation of voltage-gated channels, regenerating the full amplitude of the action potential at each point along the axon.

20. What is the definition of the equilibrium (Nernst) potential $E_{ion}$ for a given ion?

    The $V_m$ at which net flux of that ion is $0$. The equilibrium potential balances the chemical driving force from concentration gradients with the electrical driving force, resulting in zero net ion movement.

21. What is the net ion movement per cycle of the $\text{Na}^+/\text{K}^+$ ATPase?

    $3\ \text{Na}^+$ out and $2\ \text{K}^+$ in (net $+1$ out). Each cycle hydrolyzes ATP to export three sodium ions and import two potassium ions, contributing to the membrane potential by net positive charge efflux.

22. What is the absolute refractory period defined by in voltage-gated $\text{Na}^+$ channels?

    Period when inactivated $\text{Na}^+$ channels cannot reopen. During this period, sodium channels remain in an inactivated state, preventing further action potentials regardless of stimulus strength.

23. What is the typical threshold membrane potential for initiating an action potential?

    Approximately $-55\ \text{mV}$ (cell-type dependent). Threshold is the voltage at which voltage-gated sodium channels open sufficiently to trigger regenerative depolarization in the action potential.

24. State the Nernst equation for an ion of valence $z$ using natural logarithms.

    $E=\frac{RT}{zF}\ln\left(\frac{[\text{out}]}{[\text{in}]}\right)$. The Nernst equation calculates the reversal potential based on temperature, valence, and the ratio of extracellular to intracellular ion concentrations.

25. What is the primary electrogenic pump that maintains $\text{Na}^+$ and $\text{K}^+$ gradients in neurons?

    $\text{Na}^+/\text{K}^+$ ATPase. The Na+/K+ ATPase actively transports sodium out and potassium in, using ATP to maintain steep ion gradients across the neuronal membrane.

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