Human Physiology: Physiology of Excitable Cells

BIOS 3755: Human Physiology

Spring 2026

Physiology of Excitable Cells

Hodgkin AL, Huxley AF. 1939

Learning Objectives

1. Relationship Discussion: Discuss the relationship between membrane capacitance and the generation of electrotonic potentials.

2. Types of Electrotonic Potentials: List the three types of physiologic electrotonic potentials and describe their functions.

3. Mechanisms Understanding: Understand the mechanism underlying the resting membrane potential and the action potential.

4. Concentration Changes Effects: Describe how changes in sodium and potassium concentrations and membrane conductances affect the resting and action potential.

5. Action Potential Conduction: Understand how the action potential is conducted down the axon and explain the factors that affect the action potential conduction velocity.

Function and Mechanism

• Membrane Potentials

• Electrotonic Potentials

• Graded Potentials

• Action Potentials

Key Concepts

• Membrane capacitance

• Equilibrium potential

• Membrane permeability

• Current flow

Action Potential Conduction

• Determinants of conduction velocity

• Effects of Myelin

• Saltatory Conduction

• Refractory Periods

What is a Membrane Potential?

• Definition: Cells maintain an electrical potential across their cell membrane, with the inside of the cell being electrically negative relative to the fluid surrounding it.

Functions of Membrane Potential

1. Signaling: Changes in membrane potential can act as signals.

2. Transport: Electrical potential can be a source of energy for transporting substances across the membrane.

Resting Membrane Potentials of Various Cell Types

Conclusion

• All Cells Maintain a Membrane Potential, but Only Some Cells are Excitable.

What is an “Excitable Cell”?

• Definition: Excitable cells change their membrane potential as a means of communication (signaling).

Mechanisms of the Resting and Action Potentials

• General Mechanism:

  • The general mechanism of resting potential applies to all cells.

  • The general mechanism of action potential applies to all excitable cells, with specifics varying.

Neuron Structure

• Dendrites: Input from other neurons.

• Axon Hillock: Integrates information.

• Initial Segment: Integration and action potential generation.

• Axon: Conducts action potentials.

• Axon Collaterals: Communication with additional neurons.

• Axon Terminals: Output to neurons/organs.

Current and Electrical Terms

• Current: In wires, current is carried by electrons; in solutions, current is carried by ions.

  • Unit: Ampere (A)

• Resistor: Current moves through resistors.

  • Unit: Ohm (Ω)

• Electrical Potential: Energy needed to move a charge against an electric field.

  • Unit: Volt (V)

Ohm’s Law

• Equation: V = IR

  • Where R = resistance in Ohms, V = potential difference in Volts, I = current in Amperes.

Important Note:

• Remember: Know Ohm’s Law!

Membrane Characteristics

• Semipermeable Membrane: Allows unequal distribution of ions across the cell membrane.

Ion Concentration Gradients in Typical Mammalian Cells

Generation of a Membrane Potential

• Charge Separation: Generates an electrical potential.

  • Equation: V = \frac{Q}{C}

  • Voltage = Charge/Capacitance.

• Note: Biological membranes have very low capacitance; a small separation of charge produces a large potential.

Membrane Potential Types (mV)

• 0 mV: Resting Membrane Potential

• Depolarization: Less negative

• Hyperpolarization: More negative

• Overshoot: Above 0 mV

Passive Electrical Properties (Cable Theory)

• Membrane as Capacitor: Membrane stores charge, can be charged or discharged.

• Electrotonic Potential: Charge spread over the membrane, known as electrotonic potential; graded potentials are electrotonic potentials, dying away with distance from the site of initiation.

  • Distance Measurement: Length constant \lambda.

Graded Potentials

• Definition: Passive, sub-threshold; below the threshold needed to initiate an action potential.

Characteristics of Graded Potentials

• Amplitude is proportional to the stimulus strength.

• Can be depolarizing or hyperpolarizing.

• Capable of summation (temporally and spatially).

• Passive spread uniformly in all directions.

• Decay with distance from the origin.

Types of Graded Potentials

1. Postsynaptic Potentials: Result from neurotransmission.

   • EPSPs: Excitatory postsynaptic potentials.

   • IPSPs: Inhibitory postsynaptic potentials.

2. End Plate Potentials (EPPs): Occur at the neuromuscular junction.

3. Receptor Potentials: Occur in specialized sensory receptor cells.

Electrotonic Potentials: Length Constant (λ)

• Definition: Length constant describes how far an electrotonic potential spreads before dissipating.

  • Typical value: \lambda = 1-2 \text{ mm}.

• Factors Influencing Length Constant:

  • Larger membrane resistance decreases current leakage.

  • Smaller internal resistance enhances the movement of current down the axon.

Resting and Action Potential Mechanisms

• Membrane Potential maintenance: All cells maintain a resting membrane potential; excitable cells generate action potentials.

  • Cell Types: Neurons, muscle cells (skeletal, cardiac, smooth), and some endocrine cells are defined as excitable.

Overshoot and Duration of the Action Potential

• Key Facts:

  1. Action potentials overshoot 0 mV and briefly become positive.

  2. Duration of action potentials is approximately 1 ms (millisecond).

Generation of a Diffusion Potential

• Setup: A water-filled chamber is divided by a semipermeable membrane that is permeable to K+ but impermeable to A- ions.

Step-by-Step Mechanism

1. Equal concentration of KA salt in both compartments at start.

2. Add additional KA to compartment 1, leading to K+ diffusion.

3. K+ diffuses down its concentration gradient into compartment 2.

4. [Extra A-] in compartment 1 results in it being more negatively charged compared to compartment 2.

5. This negative electrical potential attracts K+ back to compartment 1.

Equilibrium Potential

1. Condition: Net movement of K+ stops when the driving force from the concentration gradient equals the driving force from the electrical gradient pulling K+ back.

2. This potential is known as the Potassium Equilibrium Potential (EK).

3. Nernst Equation to calculate Equilibrium Potentials:

   • Ex = \frac{2.3RT}{zF} \log \frac{[X]{out}}{[X]_{in}}

   • Where : R = gas constant, T = temperature in K, z = valance, F = Faraday’s constant.

Equilibrium Potentials at Body Temperature (37°C)

• Nernst Equation for monovalent cations:

  • Ex = 61 \log \frac{[X]{out}}{[X]_{in}}

  • Examples:

  • E_{Na} = +60 ext{ mV}

  • E_{K} = -90 ext{ mV}

• Resting Membrane Potential: -70 mV

RMP Near Potassium Equilibrium Potential

• Reason: The semipermeable membrane contributes to the RMP being near EK.

Conditions for Equilibrium Potential's Influence

1. Membrane must be permeable to that ion.

2. Vm ≠ Ei (membrane potential must differ from equilibrium potential).

Characteristics of RMP and Ion Permeability

• RMP is close to EK due to relatively higher K+ permeability at rest.

Balance of Ion Influences on RMP

• The resting membrane potential is a balance of the significant hyperpolarizing influence of K+ and a slight depolarizing influence of Na+.

Function of Membrane Potential (Vm)

• Membrane potential (Vm) is a function of the ion concentration gradients (K+, Na+, Cl-) and their respective permeabilities (P) across the membrane.

• Goldmann Equation: Predicts the steady-state membrane potential:
  Vm = \frac{2.3RT}{F} \log \frac{P{K}[K]o + P{Na}[Na]o + P{Cl}[Cl]i}{P{K}[K]i + P{Na}[Na]i + P{Cl}[Cl]_o}

Ion Channels and Their Role

• Ion Channels: Physical manifestations of the permeabilities in Goldmann equation; include:

  • PNa (Sodium permeability)

  • PK (Potassium permeability)

  • PCl (Chloride permeability)

Characteristics of Voltage-Gated Ion Channels

• Inactivation Gate: Many voltage-gated sodium channels have an inactivation gate, causing them to close after being opened

Channel States

• States:

  • Closed: Channel is in a resting state.

  • Open: Channel is conducting.

  • Inactivated: Non-conducting state.

Resting Membrane Potential Characteristics

• Typical RMP: Between -60 mV to -80 mV.

• Maintaining Unequal Ion Distribution: Results due to semipermeable membrane and higher K+ permeability at rest leads to RMP near EK.

Characteristics of Action Potentials

• Nature of Action Potential:

  • Regenerative and propagated wave of membrane depolarization.

  • Exhibits all-or-none response.

  • Brief duration (~1 ms in nerve).

  • Travels at a constant velocity.

  • Typical RMP of about -70 mV in nerve.

  • Overshoot to about +20 to +30 mV.

  • Involves absolute and relative refractory periods.

Action Potential Dynamics

• Depolarization Phase: Open sodium channels (increases PNa), moves Vm towards ENa.

• Repolarization Phase: Close sodium channels (decrease PNa) and open potassium channels (PK), moves Vm towards EK.

Stages in Action Potential

1. Threshold: -50 mV triggers AP.

   • Resting potential checks at -100 mV.

2. Membrane Potential Changes with Time: Diagram representation of voltage change depicts resting, threshold, and overshoot.

TTX and its Effects

• Tetrodotoxin (TTX): When applying 300 nM TTX, nerve stimulation fails to evoke an action potential.

Symptoms of TTX Poisoning:

1. Initial symptoms within 10 min to 6 hours:

   • Paresthesia of lips, face, and extremities.

   • Feelings of lightness, profuse sweating, dizziness.

   • Abdominal pain and motor dysfunction.

2. Later symptoms:

   • Spreading paralysis, dyspnea, arrhythmia, hypotension.

   • Can lead to coma, seizures, respiratory arrest, with a typical fatal outcome in 4-8 hours.

Role of Chloride in Neurons

• Function: Many neurons possess Cl- transporters that transport Cl- out of neuron.

Consequences of Cl- Movement

• Increased [Cl-]o/[Cl-]i results in ECl becoming more negative than Vm.

• Opening Cl- channels will hyperpolarize the neuron's membrane potential, important for inhibitory neurotransmitter functions.

Generation and Conduction of Action Potential

1. Initiation: Excitatory neurotransmitter binds to receptors on dendrites causing EPSPs, leading to a subthreshold passive depolarization.

2. Summation: EPSPs spread across the neuron and summate at the axon hillock.

3. Threshold Reached: If the membrane reaches activation threshold (about -55 mV), Na+ channels open.

4. Na+ Influx: Na+ flows into the neuron, causing Vm to approach ENa.

5. Na+ Channel Inactivation: Na+ channels begin to inactivate while K+ channels open, resulting in membrane repolarization.

6. Restoration: Na+/K+ pump restores Na+ and K+ concentration gradients.

Refractory Periods

• Absolute Refractory Period: No second action potential can be triggered regardless of stimulus strength.

• Relative Refractory Period: A second action potential can only be triggered by stronger stimulation.

Explanation for Refractory Periods

• Voltage-gated sodium channels become inactivated after briefly opening, requiring the membrane potential to return to resting before becoming available again.

Axonal Conduction Process

• Mechanism Details:

  • Segment of membrane depolarizes, the membrane potential reaches a threshold to open Na+ channels, causing a rapid influx of Na+ and potential overshoot.

  • Action potential travels down the axon, as Na+ channels in the resting state can still be activated.

  • The process repeats for every segment of the membrane.

Determinants of Action Potential Conduction Velocity

• Influencing Factors:

  • Axon Diameter: Larger diameter usually results in increased velocity as it's easier for current to spread within the axon.

  • Membrane Resistance: Higher resistance allows currents to travel down the axon rather than leaking out.

Summary of Axonal Conductivity

• Small unmyelinated axons: Slowest conducting.

• Large myelinated axons: Fastest conducting.

Myelination Characteristics

• Influence of Myelination:

  • Myelination increases membrane resistance; facilitated by oligodendrocytes (CNS) and Schwann cells (PNS).

  • Myelin sheath insulates axons, allowing for saltatory conduction, where action potentials are regenerated at nodes of Ranvier.

Visual Representation of Action Potential Propagation

• Mechanism of Saltatory Conduction:

  • Action potentials regenerate at nodes of Ranvier where myelin insulation triggers faster conduction through local current flow that depolarizes adjacent nodes.

Duties of Nodes of Ranvier

• Active node at peak of action potential; adjacent inactive node's depolarization eventually leads to threshold activation.

• Previous active node returns to resting potential, ceasing activity, while neighboring nodes prepare for action potential propagation.

Summary of Absolute and Relative Refractory Periods

• Detailed understanding of absolute and relative refractory periods is key to understanding action potential generation and propagation processes.