Membrane Potentials and Action Potentials

Fundamentals of Membrane Potentials

• Definition of Membrane Potential: Membrane potential refers to the electrical energy difference measured between the internal environment and the external environment of a cell. This difference is expressed in millivolts ($mV$).
• Ubiquity of Electrical Potentials: Electrical potentials are not restricted to specific systems but occur across the membranes of every cell within the human body.
• Excitable Cells: In specific types of cells known as excitable cells—most notably nerve and muscle cells—the membrane potential can evolve into action potentials. These action potentials are the primary mechanism for triggering cellular excitation.

The Action Potential (AP)

• Role in Signaling: Action potentials (APs) represent the fundamental mechanism through which neurons transmit signals across long distances. This involves both the generation and the propagation of the electrical impulse.
• Technical Definition: An action potential is characterized as a very rapid, transient change in the membrane potential that occurs when a nerve cell membrane receives adequate stimulation.
• Threshold Stimulus: For an action potential to be evoked, the stimulus must reach a minimum magnitude known as the threshold stimulus. If the stimulus does not reach this minimum strength, an action potential will not be triggered.
• Timeframe: The entire event of an action potential is high-speed, concluding within a duration of just a few milliseconds ($ms$).

Phases and Ionic Mechanisms of the Action Potential

• Initial Resting State:

  • During the resting potential state, the membrane is at approximately $-70\,mV$.
  • Physiologically, some potassium ($K^+$) leak channels remain open, while the voltage-gated sodium ($Na^+$) channels remain closed.

• Depolarization Phase:

  • Stimulus Inception: An excitatory stimulus triggers the opening of some voltage-gated $Na^+$ channels in the neuron.
  • Ion Flux: Sodium ions ($Na^+$) diffuse into the cell through these channels, moving along their electrochemical gradient.
  • Positive Feedback Loop: As the membrane potential reaches the threshold level, a "vicious circle" of positive feedback is initiated. This process causes more $Na^+$ channels to open, allowing a massive influx of $Na^+$ ions.
  • Peak Potential: The membrane potential continues to rise until it reaches a peak of approximately $+35\,mV$ (though some models also reference $+30\,mV$).

• Phase Transition and Sodium Inactivation:

  • Once the potential reaches approximately $+35\,mV$, the voltage-sensitive inactivation gates of the sodium channels close.
  • This physical closure prevents any further influx of sodium ions into the cell.

• Repolarization Phase:

  • Potassium Channel Activation: Voltage-gated potassium ($K^+$) channels open.
  • Efflux of Ions: A large outward movement of $K^+$ ions occurs, driven by the potassium concentration gradient and bolstered initially by the positive electrical gradient inside the cell.
  • Potential Reversal: This rapid loss of positive ions causes the internal environment of the membrane to return toward a negative state.

• Hyperpolarization Phase:

  • Undershoot: The significant outward current of $K^+$ ions through the open voltage-gated channels often causes a temporary "undershoot" of the electrical gradient.
  • Internal Negativity: During this phase, the interior of the neuron becomes even more negative relative to the exterior than the standard resting potential level.

• Re-establishment of Resting Potential:

  • The sodium-potassium pumps ($Na^+/K^+$ pumps) work continuously to transport sodium ions out and potassium ions in.
  • This active transport prevents long-term depletion of the ion gradients and returns the membrane to its baseline resting potential of $-70\,mV$.

Role of Additional Ions in Muscular Tissue

• Cardiac and Smooth Muscle Dynamics: Unlike standard nerve tissue, cardiac and smooth muscles utilize both voltage-gated $Na^+$ channels and voltage-gated Calcium ($Ca^{2+}$) channels.
• Slow Channels: These channels are classified as "Slow channels" because they activate after a specific time delay following depolarization.
• Smooth Muscle Specialization: In particular types of smooth muscle, the depolarization phase is exclusively caused by the opening of these slow $Ca^{2+}$ channels.

Physiological Properties of Action Potentials

• The All-or-None Law: Action potentials are characterized by the "all or none" principle. This states that the tissue will either produce a maximal response to a threshold stimulus or will produce no response at all. There is no such thing as a partial action potential.
• Refractory Periods: Tissues exhibit periods during and after an action potential where their sensitivity to subsequent stimuli is altered.

Refractory Periods in Detail

• Absolute Refractory Period:

  • Duration: This period exists from the very beginning of the depolarization phase until the first one-third of the repolarization phase has been completed.
  • Response Constraint: It is impossible to elicit a second response during this time, regardless of how strong the second stimulus might be.
  • Mechanism: All sodium ($Na^+$) channels are already activated or occupied by the first stimulus, leaving no channels available to respond to a new stimulus.

• Relative Refractory Period:

  • Duration: This occurs during the later stages of the repolarization phase.
  • Response Constraint: An action potential can be triggered, but only if the second stimulus is significantly stronger than the initial threshold stimulus.
  • Mechanism: During this time, enough $Na^+$ channels have reset to their recruitable state to allow for a new excitation, provided the stimulus is sufficiently powerful.

Electrotonic Potentials

• Characteristics: Unlike action potentials, electrotonic potentials are short-lived, localized changes in the membrane potential.
• Magnitude Decay: The resulting current flows decrease in magnitude as they travel further from the point of origin (decremental conduction).
• Stimulus Proportion: These potentials are graded; a stronger stimulus results in a greater change in voltage and a farther reach of the current flow.
• Polarity: Electrotonic potentials can be either depolarizing (making the inside less negative) or hyperpolarizing (making the inside more negative).
• Reaching the Firing Level: As the strength of the current increases, the response grows. When the depolarization reaches a range of $7$ to $15\,mV$ (bringing the potential to approximately $-55\,mV$), the firing level is achieved, and a full action potential is triggered.

Supplemental Resources

• Primary Reference: Guyton, Textbook of Medical Physiology.
• Secondary Reference: W.F. Ganong, Review of Medical Physiology.