Action Potentials: Mechanism, Propagation, and Clinical Correlations

RMP Generation: The RMP is established by:
- The movement of ions via active transport.
- The trapping of anions (proteins) within the cell.
Contributing Factors: A charge difference of $-70 \text{ mV}$ is generated by:
- The presence of both electrical and concentration gradients.
- Differences in membrane permeability to specific ions.
Key Ions: Potassium (K^+}) and sodium (Na^+}) are primarily responsible for maintaining this charge difference.

AP Curve Analysis: Draw and/or label a typical action potential curve (mV vs. time), identifying: RMP, AP Subthreshold potentials, Depolarization, Repolarization, Hyperpolarization, and refractory periods.
Ion Channel Mechanism: Explain all the above sub-points in terms of sodium and potassium channel activity.
"All or Nothing" Principle: Explain this principle of AP propagation and the role of summation.
Nerve Transmission Speed: Differentiate between slow and fast nerve transmission and the role of myelin sheaths.
Affected AP Generation: Discuss how AP generation is impacted in Multiple Sclerosis (MS) and by local anesthetics like Lignocaine.

Causes of RMP Alteration: Changes in the RMP can result from:
1. Anything that modifies ion concentrations across the membrane.
2. Anything that alters the membrane's permeability to any ion.
Neuronal Communication: Neurons transmit information as electrical signals by manipulating the membrane permeability of axons, thereby creating a current from ion flow.

Definition: APs are the primary means by which nerves transmit electrical signals along axons and how electrical signals move across the surface of muscle tissues.
Excitable Tissues: Tissues that can transmit electrical signals in this manner (nerves, muscles) are described as 'excitable'. Other tissues do not possess this capability.

Action Potential Threshold: This is a critical term that should be identifiable on an AP graph.

These terms describe the state of the membrane potential:

RMP (Resting Membrane Potential): Describes a polarized membrane, a state that exists in all living cells.
Depolarization: A decrease in the potential difference between the inside and outside of the cell. The inside of the cell becomes less negative than at RMP.
Hyperpolarization: An increase in the potential difference between the inside and outside of the cell. The inside of the cell becomes more negative than at RMP.
Repolarization: The process of returning to the RMP from either a depolarized or hyperpolarized state.
Overshoot: Occurs when the inside of the cell becomes positive ( $+ve$ ) due to the reversal of the membrane potential polarity.

Neurons generate and transmit electrical signals through specific mechanisms involving changes in membrane potential.

Communication: Neurons utilize changes in their membrane potential as vital communication signals by generating APs that can propagate along axons.
Primary Cause: Normally, changes in membrane potential are a direct result of altered membrane ion permeability.
Hypothetical Scenarios:
- Question: What would happen to the RMP if Potassium ( $[K^+]$ ) left the Intracellular Fluid (ICF)?
- Answer (Implied): The membrane would become more negative (hyperpolarize) as positive charges exit, increasing the potential difference across the membrane.
Types of Potentials: There are two main types of membrane potentials:
1. Action Potentials (APs)
2. Graded (or subthreshold) Potentials

Normal State: Diffusion gradients tend to move sodium (Na^+}) into cells, but under normal RMP conditions, very little $Na^+$ enters because membrane permeability to sodium is low.
Hypothetical Scenario: What would happen if $Na^+$ channels in the membrane were opened?
Consequence: $Na^+$ would rapidly influx into the cell, making the inside substantially more positive. If enough $Na^+$ entered, the inside of the cell could even become positive with respect to the outside, reversing the normal RMP polarity (Overshoot).

Weak Stimuli: Weak stimuli allow some $Na^+$ to enter the cell, but not in sufficient quantities to generate enough charge to open adjacent voltage-gated $Na^+$ channels and propagate an AP.
Localized Depolarization: These small, localized depolarizations are termed subthreshold or graded potentials.
Initiation of APs: If enough graded potentials reach the axon hillock from the dendrites, they can summate to collectively initiate an Action Potential in the axon.

Decremental Conduction: Graded potentials lose their strength as they propagate through the cell. This is due to the leakage of charge across the membrane (analogous to a leaky water hose).
Proportionality to Stimulus: The strength of graded potentials is directly proportional to the strength of the triggering event; a stronger stimulus produces a larger graded potential.

(a) Depolarization: A small patch of the membrane depolarizes.
(b) Spread of Depolarization: Opposite charges attract, creating local currents that depolarize adjacent membrane areas, thus spreading the wave of depolarization.
(c) Signal Decay: The membrane potential decays with distance from the stimulus because current is lost through the