Comprehensive Physiology Notes: Membrane Potentials, Graded Potentials, Action Potentials, and Ion Dynamics

Chemical and Electrical Driving Forces in Cellular Physiology

• Definition of Charged Ions:

  • Cations: Positively charged ions. Memory aid: Cats have "paws" (positive), or seeing cute cats gives a positive feeling.
  • Anions: Negatively charged ions.

• Driving Forces Governing Ion Movement:

  • Chemical Driving Force: Driven by solute concentration gradients. Ions move passively from areas of higher concentration to areas of lower concentration.
  • Electrical Driving Force: Driven by charge separation across the plasma membrane. Opposite electrical charges attract each other across the membrane (intracellular fluid vs. extracellular fluid).
  • Electrochemical Driving Force: The combined net force resulting from both chemical and electrical driving forces acting on a specific ion. The overall direction of net ion movement depends on the relative magnitudes and directions of both forces.

• Membrane Potential ($V_m$):

  • Represents the difference in electrical charge (voltage) between the intracellular fluid (ICF) and extracellular fluid (ECF).
  • Measured as potential energy stored across the plasma membrane due to separated charges lining the inner and outer membrane surfaces.
  • Equilibrium Potentials for Individual Ions:
  • Potassium ($K^+$) Alone: Yields a membrane potential of $-94\,\text{mV}$ (also referenced in general overview contexts as $-90\,\text{mV}$).
  • Sodium ($Na^+$) Alone: Yields a membrane potential of $+60\,\text{mV}$.
  • Resting Membrane Potential ($RMP$): Exactly $-70\,\text{mV}$ in a resting neuron.
  • Mechanism: $-70\,\text{mV}$ is achieved because the plasma membrane at rest is significantly more permeable to $K^+$ than to $Na^+$ due to a much higher density of open potassium leak channels.
  • Excitable Cells: Neurons and muscle cells (skeletal, smooth, cardiac) are classified as excitable because they can undergo rapid, transient (temporary) changes in their membrane potential in response to stimuli.

Types and Properties of Membrane Ion Channels

• Leak Channels:

  • Location: Distributed continuously all throughout the neuron (soma, dendrites, axon).
  • State: Permanently open at all times.
  • Function: Responsible for setting and maintaining the resting membrane potential ($-70\,\text{mV}$). Allow $Na^+$ and $K^+$ to diffuse continuously down their respective concentration gradients.

• Ligand-Gated Ion Channels:

  • Location: Highest density in the dendrites and soma (cell body), where synaptic input is received.
  • Mechanism: Open or close specifically when a chemical ligand (such as a neurotransmitter) binds to its receptor on the channel protein.
  • Function: Mediate graded potentials by permitting selective passage of ions (e.g., $Na^+$, $K^+$, or $Cl^-$).

• Voltage-Gated Ion Channels:

  • Location: Distributed along the axon, with the highest concentration located at the axon hillock (the "trigger zone" where the soma connects to the axon).
  • Mechanism: Open or close in direct response to changes in membrane potential ($V_m$).
  • Structural Gates of Voltage-Gated $Na^+$ Channels:
  • Activation Gate: Closed at resting membrane potential ($-70\,\text{mV}$). Opens rapidly upon reaching threshold voltage ($-55\,\text{mV}$), allowing rapid $Na^+$ influx. Closes during repolarization.
  • Inactivation Gate: Open at resting potential. Closes automatically at peak depolarization ($+30\,\text{mV}$) to stop $Na^+$ influx. Remains closed during repolarization and after-hyperpolarization until the membrane potential returns near resting value.
  • Requirement: Both the activation and inactivation gates must be open simultaneously for $Na^+$ ions to pass through the channel.
  • Structural Gates of Voltage-Gated $K^+$ Channels:
  • Feature a single gate that is slow to open and slow to close.
  • Triggered to open when threshold ($-55\,\text{mV}$) is reached, but full opening is delayed until peak depolarization ($+30\,\text{mV}$).
  • Slow closure past resting potential causes transient after-hyperpolarization.

• Sodium-Potassium ATPase Pump ($Na^+/K^+$ Pump):

  • Type: Active transport multiunit channel requiring energy (ATP cleavage).
  • Stoichiometry and Direction: Actively transports $3\,Na^+$ ions OUT of the cell for every $2\,K^+$ ions brought IN to the cell.
  • Function: Moves ions against their concentration gradients to maintain baseline ion distribution and restore baseline concentrations following action potentials.

Terminology of Membrane Potential Alterations

• Polarization: The condition where the membrane potential is non-zero ($-70\,\text{mV}$ at rest).
• Depolarization: An upward deflection on a voltage trace; the membrane potential becomes less negative / less polarized (moving from $-70\,\text{mV}$ toward $0\,\text{mV}$ and up to $+30\,\text{mV}$).
• Repolarization: A downward deflection on a voltage trace; the membrane potential returns back toward the resting baseline ($-70\,\text{mV}$) following depolarization.
• Hyperpolarization (After-Hyperpolarization): A downward deflection below resting potential; the membrane potential becomes more negative / more polarized than at rest (e.g., dropping to $-75\,\text{mV}$ or $-80\,\text{mV}$).

Graded Potentials and Synaptic Summation

• Properties of Graded Potentials:

  • Small, localized fluctuations in membrane potential occurring primarily at the dendrites and soma.
  • Initiated by neurotransmitter binding to ligand-gated ion channels.
  • Graded: Amplitude varies directly with the strength of the initiating stimulus.
  • Decremental: Signal magnitude decays exponentially as it travels along the cell membrane away from the site of origin.
  • Types:
  • Excitatory Graded Potentials: Depolarizing signals that shift $V_m$ closer to threshold.
  • Inhibitory Graded Potentials: Hyperpolarizing signals that shift $V_m$ further away from threshold. Equal depolarizing and hyperpolarizing signals mathematically cancel each other out.

• Summation Mechanisms at the Axon Hillock:

  • Temporal Summation: High-frequency repetitive signals arriving rapidly in time from a single presynaptic neuron source.
  • Spatial Summation: Multiple signals arriving simultaneously in space from different presynaptic neuron sources.
  • Subthreshold Stimuli: Summed graded potentials that fail to reach threshold ($-55\,\text{mV}$) at the axon hillock; no action potential is triggered.
  • Suprathreshold Stimuli: Summed graded potentials that reach or exceed threshold ($-55\,\text{mV}$) at the axon hillock; triggers an action potential.

Action Potentials: Fundamental Principles, Phases, and Steps

• Key Characteristics:

  • All-or-None Law: An action potential occurs completely once threshold ($-55\,\text{mV}$) is met, or does not occur at all if threshold is not reached.
  • Constant Amplitude: Always reaches a peak of $+30\,\text{mV}$ (spanning $-70\,\text{mV}$ to $+30\,\text{mV}$). A suprathreshold stimulus does not produce a larger or taller action potential.
  • Non-Decremental: Maintains constant amplitude and strength across the entire length of the axon.
  • Duration: Highly rapid process lasting approximately $1\,\text{ms}$.

• The 3 Major Phases and 9 Detailed Steps of an Action Potential:

  • Step 1: Resting State: Membrane potential is at resting membrane potential ($-70\,\text{mV}$).
  • Step 2: Depolarizing Stimulus: Summation of graded potentials at the soma/dendrites spreads toward the trigger zone.
  • Step 3: Reaching Threshold: Membrane at the axon hillock depolarizes to the threshold voltage of $-55\,\text{mV}$.
  • Step 4: Rapid Depolarization Phase (Phase 1): Voltage-gated $Na^+$ channels open (activation gates open rapidly). $Na^+$ rushes into the cell ($Na^+$ influx) down its electrochemical gradient in a positive feedback loop. Voltage-gated $K^+$ channels are triggered to open but respond slowly.
  • Step 5: Peak Depolarization: Voltage reaches peak at $+30\,\text{mV}$. Voltage-gated $Na^+$ channel inactivation gates close abruptly, terminating $Na^+$ influx. Voltage-gated $K^+$ channels are now fully open.
  • Step 6: Repolarization Phase (Phase 2): $K^+$ rushes out of the cell ($K^+$ efflux, e for exit) down its electrochemical gradient through open voltage-gated $K^+$ channels. $V_m$ deflects downward back toward $-70\,\text{mV}$.
  • Step 7: After-Hyperpolarization Phase (Phase 3): Voltage-gated $K^+$ channels are slow to close, allowing continued $K^+$ efflux past $-70\,\text{mV}$. The membrane becomes transiently hyperpolarized (more negative than rest).
  • Steps 8 & 9: Return to Resting Membrane Potential: Voltage-gated $K^+$ channels fully close. Passive leakage through leak channels combined with active transport via the $Na^+/K^+$ ATPase pump ($3\,Na^+$ out, $2\,K^+$ in) restores baseline resting potential ($-70\,\text{mV}$) and ionic distributions.

• Ion Movement Mnemonic:

  • "Syn and Pout" (or "Nay and Pout"): Sodium IN ($Na^+$ influx during depolarization), Potassium OUT ($K^+$ efflux during repolarization). Note: 'S' represents Sodium ($Na$), not Sulfur; 'P' represents Potassium ($K$), not Phosphorus.

Refractory Periods

• Functional Significance: Prevents backward propagation of action potentials and limits the maximum frequency of nerve impulses.

• Absolute Refractory Period:

  • Timing: Spans peak depolarization through the repolarization phase.
  • Mechanism: Voltage-gated $Na^+$ channels are in an inactivated state with their inactivation gates closed.
  • Effect: Absolutely no stimulus, regardless of magnitude or strength, can initiate a second action potential in this membrane segment.

• Relative Refractory Period:

  • Timing: Follows the absolute refractory period, corresponding to the after-hyperpolarization phase as $V_m$ returns toward $-70\,\text{mV}$.
  • Mechanism: Voltage-gated $Na^+$ channels have reset to their closed-but-activatable state, but voltage-gated $K^+$ channels remain partially open and $V_m$ is hyperpolarized.
  • Effect: A second action potential can be triggered, but only by a suprathreshold stimulus (a stronger-than-normal depolarizing stimulus).

Propagation of Nerve Impulses

• Mechanism of Local Current Flow:

  • Action potential generation at the axon hillock causes $Na^+$ influx.
  • Positive intracellular charges spread laterally to adjacent inactive membrane regions, depolarizing them to threshold and triggering sequential action potentials down the axon.

• Factors Influencing Conduction Velocity:

  • Axon Diameter: Axons with larger diameters conduct impulses significantly faster due to lower internal resistance to current flow.
  • Myelination Status:
  • Continuous Conduction: Occurs in unmyelinated axons. Action potentials must be generated sequentially across every adjacent micrometer of plasma membrane; conduction speed is relatively slow.
  • Saltatory Conduction: Occurs in myelinated axons. Myelin acts as an electrical insulator. Action potentials jump from one uninsulated gap (Node of Ranvier / neurofibril node) to the next; conduction speed is extremely fast.

• Myelinating Glial Cells:

  • Central Nervous System (CNS): Oligodendrocytes.
  • Peripheral Nervous System (PNS): Schwann cells (neurolemmocytes).

Clinical Pathologies, Electrolyte Imbalances, and Neurotoxins

• Demyelinating Pathologies:

  • Multiple Sclerosis (MS): Autoimmune destruction of myelin sheaths surrounding CNS neurons, resulting in progressive slowing and impairment of nerve impulse transmission.
  • Guillain-Barré Syndrome: Autoimmune demyelination affecting PNS motor neurons. Loss of myelin exposes large axon areas, dramatically slowing nerve impulse conduction.

• Systemic Potassium ($K^+$) Imbalances:

  • Hyperkalemia: Abnormally elevated blood/extracellular $K^+$ levels.
  • Physiological Impact: Partially depolarizes resting membrane potential closer to threshold ($-55\,\text{mV}$). Consequently, subthreshold stimuli become abnormally capable of triggering action potentials.
  • Hypokalemia: Abnormally decreased blood/extracellular $K^+$ levels.
  • Physiological Impact: Hyperpolarizes resting membrane potential further away from threshold. Normal depolarizing stimuli become less likely or unable to trigger action potentials.

• Exogenous Neurotoxins:

  • Tetrodotoxin (TTX):
  • Source: Delivered via spines/organs of the pufferfish.
  • Mechanism: Specifically blocks voltage-gated $Na^+$ channels, preventing $Na^+$ influx and halting action potential generation.
  • Clinical Effects: Inhibits skeletal and cardiac muscle contraction, leading to respiratory failure, cardiac arrest, and death.
  • Dendrotoxin:
  • Source: Venom of the Black Mamba snake.
  • Mechanism: Specifically blocks voltage-gated $K^+$ channels, preventing membrane repolarization.
  • Clinical Effects: Prevents muscle relaxation, leading to hyper-excitability, violent convulsions, muscle paralysis, and death.

Comprehensive Comparison: Graded Potentials vs. Action Potentials

• Location:

  • Graded Potentials: Soma and dendrites.
  • Action Potentials: Axon hillock (trigger zone) and along the length of the axon.

• Types of Channels Involved:

  • Graded Potentials: Ligand-gated ion channels.
  • Action Potentials: Voltage-gated $Na^+$ and $K^+$ channels.

• Voltage Change / Amplitude:

  • Graded Potentials: Variable/graded magnitude depending on stimulus strength; range from fraction of a millivolt up to threshold.
  • Action Potentials: Constant amplitude (All-or-None); always reaches $+30\,\text{mV}$.

• Conduction / Distance Properties:

  • Graded Potentials: Decremental (decays over short distances).
  • Action Potentials: Non-decremental (propagates long distances without losing signal strength).

• Summation Capability:

  • Graded Potentials: Can undergo temporal and spatial summation.
  • Action Potentials: Cannot undergo summation due to refractory periods.

• Refractory Periods:

  • Graded Potentials: Absent.
  • Action Potentials: Present (Absolute and Relative refractory periods).

Class Interactive Exercises, Dialogue, and Course Logistics

• Mnemonic & Concept Review Interaction:

  • Students established that resting membrane potential is $-70\,\text{mV}$, threshold is $-55\,\text{mV}$, and peak depolarization is $+30\,\text{mV}$.
  • Discussion of "Syn and Pout" / "Nay and Pout" for sodium influx and potassium efflux.
  • Memory trick for cations: "Cats have paws" = positive charge.

• Upcoming Schedule & Assignments:

  • Wednesday Schedule: Class ends early at 12:15 PM due to a faculty meeting (12:20 PM – 1:00 PM). Lab begins at 1:05 PM.
  • In-Class Activity: Board drawing of action potential phases and Kahoot review session scheduled for Wednesday.
  • Upcoming Quiz: Scheduled for Monday.
  • Scientific Article Reading Assignment:
  • Students must read the designated scientific paper in the course folder, answer assigned questions, and include hand drawings/diagrams.
  • Must bring a printed hard copy to lab in exactly two weeks.
  • Rule: Must be completed individually; automated AI summarization tools are strictly prohibited.
  • Lab Submissions: Complete Lab 2 packet and Post-Lab 3 due during current lab session.
  • Exam Results & Course Policy: 18 students earned "A" grades on the exam. Course policy reminder: students must achieve passing grades on both lecture exams AND lab exams to earn a final course grade of "C" or higher.