Neurophysiology Notes: Neuron Structure, Membrane Potentials, and Action Potentials

INTRA-CELLULAR AND INTER-CELLULAR TRANSMISSION

Neurons communicate using chemical (synaptic) and electrical signals.
Two main modes of transmission:
- Intra-cellular transmission: signals travel WITHIN a neuron
- Inter-cellular transmission: signals travel BETWEEN neurons via synapses
Information flow in a neuron follows a general path: input (dendrites) → integration (cell body/axon hillock) → conduction (along the axon) → output (axon terminals to other cells)
Action potential: a rapid, brief electrical signal that constitutes the main form of intracellular information transfer along the axon

NEURON STRUCTURE AND FUNCTIONAL ZONES

Dendrites: input zone where information is received
Cell body (soma) and axon hillock: integration zone where the decision to fire is made
Axon: conduction zone where information is transmitted over long distances
Axon terminals: output zone where information is transferred to other cells
Synapses: sites of inter-cellular communication; neurotransmitters are chemical messengers released at the synapse to communicate with the next neuron

NEURON MEMBRANE AND FLUIDS

Neurons have a phospholipid bilayer (cell membrane) separating intracellular fluid (cytosol) from extracellular fluid
Membrane = phospholipid bilayer; intracellular fluid is inside the cell; extracellular fluid is outside
The membrane is surrounded by fluid on both sides (primarily water)
Membrane proteins are embedded in the bilayer (hydrophilic regions face aqueous environments; hydrophobic regions span the bilayer)
Ions are dissolved in the intracellular and extracellular fluids and carry electrical charge
Ions include cations (positive charge, e.g., Na⁺, K⁺, Ca²⁺) and anions (negative charge, e.g., Cl⁻)
Negatively charged proteins are largely inside the cell and contribute to the intrinsic negativity of the resting potential

ION DISTRIBUTIONS ACROSS THE MEMBRANE (RESTING STATE)

At rest, ion concentrations differ across the membrane:
- Outside (extracellular): high Na⁺, high Cl⁻, low K⁺; typical values (outside):
- [Na⁺]ₒ ≈ 145 mM
- [K⁺]ₒ ≈ 5 mM
- [Cl⁻]ₒ ≈ 110 mM
- Inside (intracellular): high K⁺, high negatively charged proteins, low Na⁺ and Cl⁻; typical values (inside):
- [Na⁺]ᵢ ≈ 5–15 mM
- [K⁺]ᵢ ≈ 140 mM
- [Cl⁻]ᵢ ≈ 4–30 mM
Intracellular negatively charged proteins contribute to the negative intracellular environment
Ion channels and pumps regulate ion movement and concentrations across the membrane

ION MOVEMENT ACROSS THE MEMBRANE: HOW IT HAPPENS

Ions move via diffusion: from regions of high concentration to regions of low concentration (down the chemical gradient)
- Example: diffusion tends to move K⁺ out and Na⁺ in when channels are open, depending on gradients
Ions also move due to electrostatic forces (electric driving force): like charges repel, opposite charges attract
- Inside of the cell is more negatively charged than outside, creating an electrical gradient that influences ion flow
The net driving force on an ion is the electrochemical gradient, which combines chemical and electrical forces
Selective ion channels allow specific ions to move across the membrane when open
- Channels can be open or closed depending on gating mechanisms (voltage, ligands/chemicals, temperature, etc.)
- Channel proteins are embedded in the membrane

ELECTROCHEMICAL GRADIENTS AND RESTING POTENTIAL

Equilibrium potentials for key ions (approximate values shown in the lectures):
- Eᴋ ≈ -70 mV (potassium is at equilibrium with a negative inside)
- Eᴺᵃ ≈ +40 mV (sodium is at equilibrium with a positive inside when balanced)
The resting membrane potential (RMP) is typically around −60 to −70 mV, reflecting the greater permeability to K⁺ relative to Na⁺ and the activity of the Na⁺/K⁺-ATPase pump
At rest, K⁺ channels are open, Na⁺ channels are largely closed, contributing to a negative interior
The electrochemical gradient is maintained by:
- Diffusion of ions through leak channels (notably K⁺ leak channels)
- The Na⁺/K⁺-ATPase pump that uses energy to move Na⁺ out and K⁺ in against their gradients

SODIUM-POTASSIUM PUMP AND GRADIENT MAINTENANCE

Na⁺/K⁺-ATPase pump uses energy to maintain gradients by moving:
- 3 Na⁺ out of the cell for every 2 K⁺ moved in, per ATP hydrolyzed
This pump is essential to keep gradients that underlie resting potential and readiness for action potentials

RESTING MEMBRANE POTENTIAL (RMP)

Resting means no external input; neurons maintain a stable negative membrane potential
Resting membrane potential is typically in the range of $V_m \approx -60 \text{to} \ -70 \text{mV}$
Mechanisms generating RMP:
- Higher K⁺ permeability (via K⁺ channels) compared to Na⁺ permeability, pulling the potential toward Eᴋ
- Na⁺ channels remain closed, reducing Na⁺ influx at rest
- Na⁺/K⁺-ATPase maintains gradients and supports the steady state
A common teaching analogy used in lectures: a Duracell battery illustration helps visualize the inside-negative resting state

ACTION POTENTIALS: INTRACELLULAR COMMUNICATION

Action potentials are brief (transient) but large changes in membrane potential
During an AP, the interior of the neuron briefly becomes positively charged (up to about +40 mV)
The AP is typically described as an all-or-none event: once threshold is reached, an AP occurs with a consistent amplitude
The AP is initiated at the axon hillock and propagates along the axon to the terminals
Information is encoded by the frequency of action potentials, not their amplitude

PARTS OF AN ACTION POTENTIAL

Stages and key labels (as shown in the lecture figures):
- Resting state: voltage around about −70 mV (often cited as −60 to −70 mV)
- Stimulus reaches threshold: around −55 mV (threshold) → voltage-gated Na⁺ channels activate
- Depolarization: rapid Na⁺ influx raises membrane potential toward +40 mV
- Peak: interior becomes positive; Na⁺ channels begin to inactivate
- Repolarization: voltage-gated K⁺ channels open and K⁺ exits the cell, restoring negative interior
- Hyperpolarization: membrane potential briefly undershoots resting level (more negative than RMP)
- Resting state restoration: Na⁺/K⁺-ATPase and leak channels return the membrane to RMP
Notable constants from the lecture visuals:
- Threshold near −55 to −40 mV depending on slide; resting around −60 to −70 mV; peak around +40 mV
The sequence is typically summarized as: depolarization (Na⁺ in) → repolarization (K⁺ out) → hyperpolarization (brief overshoot of RMP) → reset

ION CHANNELS AND THEIR GATING

Types of ion channels involved in APs:
- Voltage-gated Na⁺ channels: open/activate at threshold, allow Na⁺ influx; start of depolarization
- Inactivation of Na⁺ channels after a brief window prevents continued Na⁺ influx (absolute refractory period)
- Relative refractory period occurs when most Na⁺ channels have returned to the closed state, but some K⁺ channels remain open
- Voltage-gated K⁺ channels: slower to open; allow K⁺ efflux to repolarize and sometimes hyperpolarize
- Other channels may be ligand-gated or temperature-sensitive, affecting channel states
The opening/closing of channels is what governs the rise and fall of membrane potential during an AP

REFRACTORIES AND RESHAPING OF THE AP

Absolute refractory period: Na⁺ channels are inactivated and cannot reopen immediately; another AP cannot be initiated
Relative refractory period: some Na⁺ channels have recovered, but ongoing K⁺ conductance and other factors make it harder to initiate another AP; a stronger stimulus may trigger one
After refractory periods, the neuron returns to its resting state (RMP) and can fire again if threshold is reached

INTERCELLULAR COMMUNICATION: SYNAPSES AND NEUROTRANSMITTERS

Neurons communicate with other neurons at synapses via neurotransmitters
Neurotransmitter release is triggered by the arrival of an AP at the axon terminal
The released neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane, influencing the postsynaptic membrane potential
This chemical signaling is the basis for inter-neuron communication and the integration of information in the neural network

RELATIONSHIPS AND PRACTICAL IMPLICATIONS

Electrical vs chemical signaling: APs provide fast, long-distance electrical signals along axons; neurotransmitters convert electrical signals into chemical messages at synapses
The resting and action potentials rely on gradients, selective channels, and pumps, illustrating how energy (ATP) and biophysical properties cooperate to enable neural function
The concept of the electrochemical gradient explains how both concentration differences and membrane voltage influence ion flow and neural excitability
Understanding APs helps explain many real-world neural phenomena, such as how drugs or toxins that affect Na⁺ or K⁺ channels alter nerve signaling

KEY NUMERICAL AND FORMULA ELEMENTS (WITH LaTeX)

Resting membrane potential range: $V_m \approx -60 \text{ to } \ -70 \text{ mV}$
Action potential peak: $V_m \approx +40 \text{ mV}$
Threshold potential: commonly around $V_{th} \approx -55 \text{ mV}$
Equilibrium potentials (approximate): $EK \approx -70 \text{ mV},\quad E{Na} \approx +40 \text{ mV}$
Na⁺/K⁺-ATPase pump stoichiometry: $ext{Na}^+{ ext{out}}: ext{K}^+{ ext{in}} = 3:2 ext{ per ATP}$
Ionic concentrations (typical resting state):
- [Na^+]{out} \,\=\, 145 \,\text{mM},\quad [Na^+]{in} \,\=\, 5\text{--}15 \,\text{mM}
- [K^+]{out} \,\=\, 5 \,\text{mM},\quad [K^+]{in} \,\=\, 140 \,\text{mM}
- [Cl^-]{out} \,\=\, 110 \text{ mM},\quad [Cl^-]{in} \=\, 4\text{--}30 \text{ mM}
Diffusion (chemical driving force) vs electrostatic force (electrical driving force) together form the electrochemical gradient
General relation for ion movement through channels (conceptual, not shown as a slide):
- Ion current: $I{ion} = g{ion} (Vm - E{ion})$ where $g{ion}$ is the conductance and $E{ion}$ is the equilibrium potential
Nernst-style relation (for context, not shown explicitly in every slide):
- $E{ion} \approx \frac{RT}{zF} \,\ln \left(\frac{[ion]{outside}}{[ion]_{inside}}\right)$

CONNECTIONS TO PREVIOUS AND REAL-WORLD CONTEXT

Connects foundational principles of cell biology (membrane structure, lipid bilayer, proteins) to neurophysiology (ion channels, pumps, signaling)
Demonstrates how energy use (ATP) underpins the maintenance of ion gradients essential for nerve signaling
Provides a framework for understanding how pharmacological agents that affect ion channels alter neuronal excitability and signaling
Highlights why certain neurological conditions can arise from disruptions in ion gradients, channels, or pump function

BRIEF SUMMARY

Neurons transmit information within cells via action potentials and between cells via synapses using neurotransmitters
The resting state is established by ion gradients and selective membrane permeability, primarily through K⁺ leak channels and the Na⁺/K⁺ pump
An action potential is triggered when depolarization reaches threshold, involving rapid Na⁺ influx followed by K⁺ efflux, with characteristic phases: depolarization, repolarization, and hyperpolarization
Refractory periods regulate firing rate and ensure unidirectional propagation of the signal
Ion concentrations, membrane potential values, and channel dynamics together determine neuronal excitability and signaling reliability