Membrane Potential and Action Potentials 1.3

Key Elements of Cellular Communication

• Cellular communication relies on three fundamental components:  - The Membrane: Acts as the physical barrier and site of electrical activity.  - Membrane Transport Proteins: Specialized structures that permit or facilitate the movement of substances.  - Fluids: The liquid environments inside and outside the cell where communication occurs.
• Electrical Signals: Controlled by the movement of ions (charged atoms) across the neuronal membrane.
• Ion Passage: The movement of ions between fluid environments is permitted via specialized channels and pumps.
• Communication Cycle: Neuronal communication follows a repetitive cycle of electrical impulses and chemical exchanges:  - Electrical Impulse $\rightarrow$ Chemical Exchange $\rightarrow$ Electrical Impulse $\rightarrow$ Electrical Impulse $\rightarrow$ Chemical Exchange $\rightarrow$ Electrical Impulse.

Neuronal Membrane Structure and Function

• Phospholipid Bilayer: The neuronal membrane is composed of a phospholipid bilayer with distinct regions:  - Hydrophilic Heads: "Water-loving" heads that face the aqueous environments (outward towards the extracellular fluid and inward towards the cytosol).  - Hydrophobic Tails: "Water-hating" tails that face each other, forming the interior of the membrane.
• Primary Functions of the Membrane:  - Isolation: Isolates the cytosol (intracellular fluid) from the extracellular fluid.  - Selective Control: Controls the movement of substances into and out of the cell.  - Electrical Insulation: Maintains the electrical properties necessary for signaling.
• Constraints on Ion Travel: Ions cannot freely cross the phospholipid bilayer due to two main factors:  - Size: Ions are often too large to pass through the tightly packed bilayer.  - Charge: The hydrophobic tails of the bilayer repel charged molecules.  - Requirement: Because of these constraints, ions must travel via specialized transport proteins.

Membrane Transport Mechanisms

• Passive Transport:  - Energy Requirement: Does NOT require energy.  - Gradient: Movement occurs ALONG the concentration gradient (e.g., from an area of high concentration to an area of low concentration).  - Types of Passive Transport:   - Simple Diffusion: Movement of small, nonpolar molecules (example: $O_2$) directly through the bilayer without the help of membrane proteins.   - Facilitated Diffusion: Movement via membrane proteins.   - Osmosis: The specific movement of $H_2O$ across the membrane.
• Active Transport:  - Energy Requirement: DOES require energy in the form of ATP (Adenosine Triphosphate).  - Gradient: Movement occurs AGAINST the concentration gradient (e.g., from low concentration to high concentration).  - Types of Active Transport:   - Ion Pumps: Proteins that use ATP to fuel the transport of ions.   - Endocytosis: Internalization of substances via structural changes to the cell membrane.   - Exocytosis: Export/secretion of substances via structural changes to the cell membrane.

Specialized Membrane Transport Proteins

• Ion Channels (Passive Transport):  - Facilitate movement down the concentration gradient.  - Leaky (Non-gated) Channels: Randomly alternate between open and closed states, though they are generally considered open.  - Gated Channels: Open or close in response to specific stimuli. Types include:   - Ligand-Gated (Chemical-Gated): Only opens in response to the binding of a specific ligand or chemical messenger.   - Voltage-Gated: Only opens or closes in response to a specific change in the membrane potential (e.g., a change to $-55\,mV$).   - Mechanically-Gated: Only opens in response to a physical force such as pressure or tension.
• Ion Pumps (Active Transport):  - Require ATP to transport ions across the membrane against their concentration gradient.  - Function to maintain specific ion distributions necessary for cellular signaling.

Cellular Fluids and Ion Distribution

• Main Ingredient: Water is the primary component of both intracellular fluid (cytosol) and extracellular fluid.
• Ions: Electrically charged atoms dissolved in water. The most important ions in cellular physiology are:  - Sodium: $Na^+$  - Potassium: $K^+$  - Calcium: $Ca^{2+}$  - Chloride: $Cl^-$
• Membrane Potential: Defined as the difference in charge between the extracellular and intracellular environments.  - Polarization: The cell is "polarized" because of the uneven distribution of ions.  - Relative Charge: The inside of the neuronal cell membrane is negatively charged compared to the outside.  - Example Calculation: If the outside has a charge of $+6$ and the inside has a charge of $+4$, the calculation is $+4 - (+6) = -2$. This means the inside is 2 units "less positive" than the outside.

The Resting Membrane Potential (RMP)

• Definition: The membrane potential (charge difference) of a neuron when it is not actively sending a signal (at rest).
• Value: The Resting Membrane Potential of a neuron is typically $-70\,mV$.
• Ionic Basis: Generated by the uneven distribution of $Na^+$, $K^+$, and negatively charged proteins.  - Higher concentration of $Na^+$ outside the cell.  - Higher concentration of $K^+$ inside the cell.
• Maintenance via the Na+/K+ ATPase Pump:  - Ions naturally want to travel down their gradients to reach equilibrium.  - To counteract this and maintain the negative rest environment, the pump actively moves ions.  - Mechanism: Pumps $3 \times Na^+$ OUT of the cell and $2 \times \text{ K}^+$ INTO the cell.  - Energy: Requires ATP to move these ions against their respective concentration gradients.

The Action Potential: Mechanics and Phases

• Key Concept: An Action Potential is a wave of positive ions moving into the neuron, traveling along the axon to the axon terminal.
• Function: Exciting a neuron allows it to communicate; the action potential leads a neuron to "fire" or send a message.
• Excitation Requirement: To excite the cell, the inside must be made more positive than the outside through a change in membrane potential.
• Threshold Requirement: An action potential is an "All or nothing" response. If the threshold is not reached, initiation fails.

Phases of the Action Potential

1. Resting Membrane Potential: The starting state where the membrane is at $-70\,mV$.

2. Threshold (Initiation):  - Chemical messages (stimuli) cause ligand-gated channels to open.  - $Na^+$ enters the cell, moving down its concentration gradient.  - Influx of positive ions makes the interior less negative.  - Threshold Value: Once the influx reaches approximately $-55\,mV$, an action potential is triggered.

3. Depolarization:  - Upon reaching the threshold, voltage-gated $Na^+$ channels open.  - A massive flood (influx) of $Na^+$ enters the axon.  - This makes the interior rapidly more positive until it reaches a peak of around $+40\,mV$.

4. Repolarization:  - Once the peak of $+40\,mV$ is achieved, the neuron must return to rest.  - Voltage-gated $Na^+$ channels close (inactivate).  - Voltage-gated $K^+$ channels open.  - $K^+$ moves down its gradient from the inside to the outside (efflux).  - Result: Positive ions ($Na^+$) stop entering, and positive ions ($K^+$) leave, making the membrane potential negative again.

5. Hyperpolarization:  - The efflux of $K^+$ ions often "overshoots" the resting potential.  - Too many $K^+$ ions rush out, making the potential even more negative than the resting state, reaching approximately $-90\,mV$.  - At $-90\,mV$, the voltage-gated $K^+$ channels close.  - Purpose: This creates a refractory period, making it difficult to achieve another action potential immediately and ensuring the signal travels in only one direction.

6. Return to Resting Membrane Potential:  - Voltage-gated $Na^+$ and $K^+$ channels are now closed.  - The Na+/K+ ATPase pump (3 $Na^+$ out / 2 $K^+$ in) restores the balance to $-70\,mV$ in preparation for the next signal.

Action Potential Conduction along the Axon

• Propagation: The action potential travels from the Soma (cell body), down the Axon, to the Axon Terminal.
• Uni-directional Travel: Depolarization spreads down the axon. Parts of the membrane behind the wave repolarize and cannot immediately depolarize again due to inactivated $Na^+$ channels and open $K^+$ channels.
• Conduction Types:  - Saltatory Conduction (Myelinated Axons):   - Depolarization occurs only at the Nodes of Ranvier (gaps between myelin segments).   - The myelin sheath maintains signal strength, allowing the depolarization to "jump" from node to node.   - This is faster and more efficient than continuous conduction.  - Continuous Conduction (Unmyelinated Axons):   - Depolarization must occur in immediately adjacent segments along the entire length of the axon.