Axon Biophysics and Action Potential Generation

Flashcards covering axon biophysics, cable model parameters, voltage-clamp studies, Hodgkin-Huxley equations, channel gating mechanisms, and action potential dynamics.

What does it mean for a neuronal membrane to depolarize?

The membrane potential becomes less negative.

What does it mean for a neuronal membrane to repolarize?

The membrane potential returns back toward its resting potential.

What does it mean for a neuronal membrane to hyperpolarize?

The membrane potential becomes more negative than its resting potential.

What did Hermann propose in 1905 regarding action potential propagation?

He proposed that potential changes in an excited region send current down the center of the axon, out through the membrane, and into the extracellular space, making action potentials self-stimulating.

What theoretical model did Hermann establish to describe the passive spread of electrical current down an axon?

Cable Theory (or the Cable Model).

How does increasing cell size affect membrane resistance ($R_m$)?

Increasing cell size decreases membrane resistance ($R_m$) because a larger cell area provides more ion leakage pathways.

How does increasing cell size affect internal axoplasmic resistance ($R_i$)?

Increasing cell size decreases the internal/axoplasmic resistance ($R_i$).

How does increasing cell size affect membrane capacitance ($C_m$)?

Increasing cell size increases membrane capacitance ($C_m$).

What is the mathematical equation for the length constant ($\lambda$) in terms of specific membrane resistance ($r_m$) and axial resistance ($r_i$)?

$$\lambda = \sqrt{\frac{r_m}{r_i}}$$

What does the length constant ($\lambda$) measure in a neuron?

It measures how far voltage changes spread passively along the length of a neuron.

What specific membrane capacitance value did K. S. Cole determine in 1938 for nerve membranes?

$$1\,\mu\text{F/cm}^2$$

How are the membrane capacitance and resistance arranged relative to each other in Cole's circuit model of the membrane?

They are connected in parallel.

What did Hodgkin demonstrate in 1935 by blocking action potential conduction with ice?

He demonstrated that passive spreading of local circuit current ahead of the action potential propagates excitation down the nerve.

What change in membrane conductance did Cole and Curtis observe during an action potential in 1939?

A $40$\text{-fold} increase in membrane conductance.

What percentage change in membrane capacitance did Cole and Curtis measure during nerve excitation?

A $2\%$ change in membrane capacitance.

What is the maximum diameter that squid giant axons can reach?

Up to $1\,\text{mm}$ in diameter.

Who recorded the first internal action potential from inside a nerve fiber using a glass microelectrode in 1939?

A. L. Hodgkin and A. F. Huxley.

What did Baker, Hodgkin, and Shaw (1962) discover by removing axoplasm from giant axons and perfusing them?

They showed that resting and action potentials are unaffected by the removal and replacement of axoplasm.

How did Hodgkin and Katz (1949) test the hypothesis that the action potential overshoot depends on $\text{Na}^+$ ions?

They reduced extracellular $\text{Na}^+$ concentration and observed a corresponding reduction in action potential amplitude.

Under what condition does the plot of resting membrane potential versus extracellular potassium concentration ($[\text{K}^+]_o$) exhibit a theoretical Nernst slope of $58\,\text{mV}$ per tenfold change?

Only at relatively high extracellular potassium concentrations.

Which cell type was shown by Kettenmann, Sonnhof, and Schachner (1983) to exhibit an exclusive potassium dependence of its membrane potential?

Cultured mouse oligodendrocytes.

What is the primary function of the voltage-clamp technique?

To control or "clamp" the membrane potential at a set value by feedback current injection while measuring the resulting ionic currents.

In voltage-clamp recordings, what defines an inward current and how is it visually displayed?

An inward current is defined as the movement of positive charge into the cell, displayed as a downward deflection.

In voltage-clamp recordings, what defines an outward current and how is it visually displayed?

An outward current is defined as the movement of positive charge out of the cell, displayed as an upward deflection.

What does Hodgkin and Huxley's Independence Relation state regarding ion movement?

It states that different ions move independently down their own individual electrochemical gradients, resulting in zero net current at each ion's Nernst equilibrium potential.

What happens to transient inward $\text{Na}^+$ current as clamp voltage steps approach the equilibrium potential for $\text{Na}^+$ ($E_{\text{Na}}$)?

The inward $\text{Na}^+$ current magnitude decreases toward zero.

What happens to steady-state outward $\text{K}^+$ current as clamp voltage increases progressively above the equilibrium potential for $\text{K}^+$ ($E_{\text{K}}$)?

The outward $\text{K}^+$ current continually increases in size.

How are macroscopic membrane currents related to single-channel (microscopic) currents?

Macroscopic currents are the ensemble average or sum of current pulses flowing through thousands of individual ion channels.

What impermeable organic cation was used by researchers to replace extracellular $\text{Na}^+$ in order to isolate $\text{Na}^+$ currents by subtraction?

Choline (choline chloride).

In the Hodgkin-Huxley equivalent electrical circuit model of a membrane, what parameter does $C_M$ represent?

The membrane capacitance.

How are the sodium and potassium pathways modeled in the Hodgkin-Huxley equivalent circuit?

As variable conductances ($g_{\text{Na}}$ and $g_{\text{K}}$) each connected in series with a Nernst electromotive force battery ($E_{\text{Na}}$ and $E_{\text{K}}$).

What is the steepness slope of the relative maximum conductance curve for $\text{Na}^+$ channels as potential increases?

$$3.9\,\text{mV/e-fold}$$

What is the steepness slope of the relative maximum conductance curve for $\text{K}^+$ channels as potential increases?

$$4.8\,\text{mV/e-fold}$$

If a membrane is maintained in a continuously depolarized state, what happens to the $\text{Na}^+$ and $\text{K}^+$ channels?

$\text{Na}^+$ channels close (inactivate), while $\text{K}^+$ channels remain open.

What term refers to the increase in membrane conductance to $\text{Na}^+$ and $\text{K}^+$ that occurs upon membrane depolarization?

Rectification.

Why does ionic current decrease near an ion's Nernst equilibrium potential even when conductance is fully maximized?

Because current depends on driving force ($I = g(V - V_{\text{eq}})$); as $V$ approaches $V_{\text{eq}}$, the driving force $(V - V_{\text{eq}})$ drops to zero.

What are the positions of the activation and inactivation gates of a voltage-gated $\text{Na}^+$ channel at resting membrane potential?

The activation gate is closed and the inactivation gate is open.

What structural transition opens a voltage-gated $\text{Na}^+$ channel during initial depolarization?

Movement of charged residues in the voltage-sensing $\alpha$ helix causes the activation gate to open.

What steps are required for an inactivated $\text{Na}^+$ channel to reset back to its resting state?

The membrane must repolarize, causing closure of the activation gate and displacement of the channel-inactivating segment so the inactivation gate re-opens.

According to Lacroix et al. (2013), how much faster are voltage-sensor module kinetics in $\text{Nav}$ channels compared to Shaker-type $\text{Kv}$ channels?

Up to $6$\text{-fold} faster.

What specific molecular feature in $\text{Nav}$ domains I–III causes a $3$\text{-fold} acceleration of voltage-sensor kinetics relative to $\text{Kv}$ channels?

The hydrophilicity of two "speed-control" residues located in the S2 and S4 segments.

How much additional acceleration of $\text{Nav}$ voltage-sensor kinetics is provided by coexpression of the $\beta1$ subunit?

An additional $2$\text{-fold} acceleration.

What is the design and purpose of a two-pulse voltage-clamp experiment?

It applies a variable prepulse followed by a test pulse to determine how prepulse voltage and time influence $\text{Na}^+$ channel inactivation and recovery.

What do the values $h = 1$ and $h = 0$ represent on a sodium channel inactivation curve?

$h = 1$ indicates $100\%$ of $\text{Na}^+$ channels are available (not inactivated), while $h = 0$ indicates $100\%$ are inactivated.

What parameter measures the time constant for recovery of $\text{Na}^+$ channels from inactivation, and what is its value at $-75\,\text{mV}$ in a Node of Ranvier?

The time constant is $\tau_h$, which is approximately $4.6\,\text{ms}$ at $-75\,\text{mV}$.

In the Hodgkin-Huxley model, why is potassium conductance expressed as $g_{\text{K}} = n^4 \bar{g}_{\text{K}}$?

Because $n^4$ represents the mathematical probability that four identical gating particles are simultaneously in the open position.

What equation expresses the sodium current ($I_{\text{Na}}$) in the Hodgkin-Huxley model?

$$I_{\text{Na}} = m^3 h \bar{g}_{\text{Na}} (E - E_{\text{Na}})$$

What defines the threshold potential (typically near $-50\,\text{mV}$) during action potential initiation?

The critical membrane potential at which regenerative opening of voltage-gated $\text{Na}^+$ channels produces an inward current that exceeds outward currents.

What channel mechanism accounts for the absolute refractory period?

Complete inactivation of voltage-gated $\text{Na}^+$ channels during the falling phase, making it impossible to elicit another action potential.

Why is a larger stimulus required to evoke an action potential during the relative refractory period?

Because although $\text{Na}^+$ channels have recovered from inactivation, the membrane is hyperpolarized below rest potential due to open $\text{K}^+$ channels.