13.1 Neuronal Anatomy, the Resting Potential & the Action Potential

13.1 Neuronal Anatomy, the Resting Potential & the Action Potential

Neuronal communication integrates electrical signaling across individual cellular membranes with chemical signaling across specialized intercellular junctions. Mastering this discipline requires tracking the movement of specific ions across lipid bilayers, calculating electrochemical gradients, and understanding the pharmacological and physiological regulation of neural circuits.

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Structural Anatomy of the Neuron

A neuron is an asymmetric, electrically excitable eukaryotic cell structurally partitioned into distinct functional domains:

• Soma (Cell Body): Contains the nucleus, extensive rough endoplasmic reticulum (Nissl bodies for high-volume protein and neuropeptide synthesis), Golgi apparatus, and mitochondria. It serves as the primary metabolic and biosynthetic hub.
• Dendrites: Highly branched, tapering cytoplasmic extensions covered in dendritic spines. Dendrites receive incoming synaptic inputs from presynaptic neurons and convey graded, decremental electrical signals toward the cell body.
• Axon Hillock: The conical region connecting the soma to the axon proper. It contains the highest density of voltage-gated sodium ($Na_V$) channels in the unmyelinated neuron and functions as the trigger zone (integrator) where graded post-synaptic potentials undergo summation. If net local potential reaches threshold, an action potential is fired.
• Axon: A singular, uniform cylindrical projection extending up to a meter in length. It propagates action potentials away from the soma toward target effector cells or subsequent neurons via continuous or saltatory conduction.
• Myelin Sheath & Nodes of Ranvier: Myelin is a lipid-rich, multi-layered insulating sheath produced by Schwann cells in the Peripheral Nervous System (PNS; one Schwann cell wraps a single internode) and by Oligodendrocytes in the Central Nervous System (CNS; one oligodendrocyte wraps internodes on up to 50 axons). The gaps between adjacent myelin segments are the nodes of Ranvier, which harbor high concentrations of $Na_V$ and $K_V$ channels.
• Axon Terminal (Synaptic Bouton): The swollen distal terminus containing abundant mitochondria, smooth endoplasmic reticulum for calcium sequestration, and membrane-bound synaptic vesicles packed with neurotransmitters.

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The Resting Membrane Potential ($V_m$)

In a quiescent neuron, an electrical potential difference exists across the plasma membrane, termed the resting membrane potential ($V_m$), typically $-70\text{ mV}$ (inside negative relative to the extracellular fluid). This electrical polarity is established and maintained by two primary mechanisms:

1. Differential Permeability and Potassium Leak Channels

The resting neuronal membrane is approximately 25 to 30 times more permeable to potassium ($K^+$) than to sodium ($Na^+$) due to the presence of continuously open, non-gated $K^+$ leak channels (two-pore domain $K^+$ channels). Potassium, maintained at high intracellular concentration (~140 mM inside vs. ~4.5 mM outside), diffuses down its chemical concentration gradient out of the cell. As positive charges exit, the interior of the cell becomes increasingly electronegative. This accumulating negative charge creates an opposing electrical force pulling $K^+$ back into the cell. Equilibrium is reached when the outward chemical driving force precisely equals the inward electrical driving force, defined by the Nernst Equation for a single ion at physiological temperature ($37^\circ\text{C} = 310\text{ K}$):

$$E_{ion} = \frac{RT}{zF} \ln\left(\frac{[ion]_{out}}{[ion]_{in}}\right) = \frac{61.5}{z} \log_{10}\left(\frac{[ion]_{out}}{[ion]_{in}}\right)$$

• For Potassium ($K^+$): $E_K = \frac{61.5}{+1} \log_{10}\left(\frac{4.5}{140}\right) \approx -90\text{ mV}$
• For Sodium ($Na^+$): $E_{Na} = \frac{61.5}{+1} \log_{10}\left(\frac{145}{12}\right) \approx +65\text{ mV}$

Because the resting membrane is predominantly permeable to $K^+$, the overall resting potential ($V_m = -70\text{ mV}$) lies close to $E_K$, as modeled mathematically by the Goldman-Hodgkin-Katz (GHK) Voltage Equation:

$$V_m = \frac{RT}{F} \ln\left(\frac{P_K[K^+]_{out} + P_{Na}[Na^+]_{out} + P_{Cl}[Cl^-]_{in}}{P_K[K^+]_{in} + P_{Na}[Na^+]_{in} + P_{Cl}[Cl^-]_{out}}\right)$$

2. The Electrogenic $Na^+/K^+$-ATPase Pump

Continuous leak of $K^+$ out of the cell and minor leak of $Na^+$ into the cell would eventually dissipate these transmembrane concentration gradients. The $Na^+/K^+$-ATPase (sodium-potassium pump) counteracts this rundown by utilizing the energy of primary ATP hydrolysis to transport $3\text{ }Na^+$ ions out of the cell and $2\text{ }K^+$ ions into the cell against their steep electrochemical gradients. Because it moves three positive charges out for every two positive charges moved in, the pump is electrogenic, contributing directly to approximately $-3\text{ to }-5\text{ mV}$ of the resting membrane potential while permanently maintaining the chemical driving forces required for excitability.

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The Action Potential: Phases, Gating Kinetics & Refractory Periods

An action potential is a rapid, transient, all-or-none allosteric electrical cycle propagated without attenuation along the axonal membrane.

Molecular Mechanics of Refractory Periods

1. Absolute Refractory Period: Spans from the initial firing at threshold through the peak and early repolarization phase. During this window, the inactivation gates ($h$-gates) of voltage-gated $Na^+$ channels are physically closed. Even a massively suprathreshold stimulus cannot open these channels because they must first undergo repolarization-dependent reset (de-inactivation). This ensures unidirectional forward propagation of the action potential and imposes an upper mathematical limit on neuronal firing frequency.
2. Relative Refractory Period: Follows the absolute refractory period during the hyperpolarization phase. At this point, the $Na_V$ channel inactivation gates have reopened ($m$-gates are closed, restoring the excitable closed state), but the delayed rectifier $K_V$ channels remain open, driving $V_m$ down toward $-80\text{ mV}$. Because the membrane is further from threshold ($-55\text{ mV}$) and membrane conductance to $K^+$ is elevated, an action potential can be initiated, but only by an exceptionally strong, suprathreshold stimulus.

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