S

Lecture 28 Action Potentials Part 2

Action Potential Overview

  • The action potential (AP) is a brief fluctuation in membrane potential.

  • It lasts a few milliseconds in axons and slightly longer in cell bodies.

  • It is caused by the transient opening of voltage-gated ion channels (mainly Na^+ and K^+).

  • AP spreads like a wave along the neuron and can also occur in muscle fibers.

Stages of the Action Potential

  • There are three key stages of the action potential:

    1. Fast depolarization to approximately +30mV (reversal of polarization or overshoot) when the membrane potential reaches threshold.

    2. Repolarization.

    3. Hyperpolarization.

Threshold

  • The stages are always preceded by a period where the cell membrane is depolarized to a threshold (typically -55 mV) by a physical or chemical stimulus.

  • The resting membrane potential may vary (for example, -70 mV instead of the standard -65 mV).

Learning Objectives

  • Describe the three stages of the action potential and associated changes in membrane permeability to Na^+ and K^+.

  • Explain molecular events leading to Na^+ channel activation and inactivation.

  • Explain how action potentials are generated by an electrical stimulus.

  • Understand the concept of passive spread of potential along the cell membrane.

  • Explain the mechanism of action potential transmission in unmyelinated and myelinated axons.

  • Explain how action potentials are generated in sensory neurons (receptor potential).

Ionic Mechanisms

  • The stages are associated with opening and closing of voltage-gated ion channels, affecting membrane permeability to Na^+ and K^+.

Condition

Event(s)

Relative permeability to ions

Resting membrane potential

See Lecture 27

PK >> P{Na} (40/1)

Depolarization to threshold

Stimulus (physical or chemical). Voltage-gated Na^+ channels start to open near threshold

(PK > P{Na})

Stage 1: Fast depolarization

Voltage-gated Na^+ channels open very fast

P{Na} >>> PK

Stage 2: Repolarization

Na^+ channels inactivate and voltage-gated K^+ channels open

PK >>> P{Na}

Stage 3: After-hyperpolarization

Voltage-gated K^+ channels remain open for a while and then close

PK >>> P{Na} then PK >> P{Na}

Activation and Inactivation of Voltage-Gated Channels

  • Local hyperpolarization and depolarization influence the state of voltage-gated Na^+ channels.

  • The process includes activation, inactivation, and return to the resting state upon membrane repolarization.

Generation of Action Potentials by Electrical Stimulation

  • Local depolarization.

  • Passive current spread (inside and outside the axon).

  • Depolarization at adjacent parts of the membrane.

Passive Spread of Current

  • Current spreads passively over a short distance.

  • The length constant (\lambda) indicates the distance at which the potential drops to 37% (\frac{1}{e}) of the initial value.

Action Potential Transmission in Unmyelinated Axons

  • Action potential is generated.

  • Passive current spread occurs.

  • Adjacent parts of the membrane are depolarized to the threshold.

  • Voltage-gated Na^+ channels are activated.

  • New action potentials are generated on both sides of the initial AP.

Action Potential Transmission in Myelinated Axons

  • Myelination increases the action potential (AP) conduction velocity.

  • It increases AP speed by enhancing the efficiency of passive spread.

  • Action potentials are generated only at the nodes of Ranvier, with current flowing passively between them (saltatory conduction).

  • The typical distance between nodes is approximately 1 mm.

Generation of Action Potentials in Sensory Neurons

  • A stimulus acting on receptors in sensory neurons evokes a graded depolarization called the receptor potential.

  • The receptor potential spreads passively to the trigger zone, where APs are generated.

  • APs spread along the axon towards the CNS.

  • Information about the strength of the stimulus is coded in the amplitude of the receptor potential and the frequency of APs.

Axons

  • Two types of axons:

    1. Unmyelinated axons: small diameter (~1 um); transmission of APs is slow and continuous.

    2. Myelinated axons: larger diameter (5-10 um); transmission of APs is fast and saltatory.

Two Stages of Action Potential Transmission

  • Passive spread

  • Generation of Action potentials

Passive Spread of Current

  • If subthreshold, depolarization occurs at one region of the membrane.

  • Passive current flows inside and outside the axon.

  • Adjacent parts of the membrane are depolarized.

Limitations of Passive Spread

  • Current can spread passively only over a short distance, typically less than 1mm.

Action Potential Transmission in Unmyelinated Axons

  • A small amount of current inside will trigger a change. Voltage-gated Na+ channels in adjacent parts of the membrane open.

  • New full-sized APs are generated in adjacent parts of the membrane

Benefit

  • The benefit of action potential is that there are full-sized action potentials regenerated at each point of the axon.

  • Regeneration occurs along the entire axon via passive current spread.

Speed of AP Transmission

  • Speed of AP transmission in unmyelinated axons is ~ 1 m/sec.

  • Passive current flow between two adjacent points is fast, but AP must be regenerated at every point on the membrane, which takes time and slows conduction velocity.

  • AP propagates much faster in myelinated axons at ~ 20 to 100 m/sec.

Structure of Neurons with Myelinated Axons

  • Myelin sheath is formed by oligodendrocytes in the CNS and Schwann cells in the PNS.

  • Myelination is discontinuous, interrupted at nodes of Ranvier.

Impact of Myelination

  • Increases passive spread of current due to the insulating properties of myelin, resulting in less current dissipation as it flows along the axon.

  • Passive conduction occurs in both directions.

Advantages of Myelination

  • Myelination increases the speed of AP conduction by increasing the efficiency of passive spread.

  • APs do not need to be regenerated at every part of the cell membrane but are generated only at nodes of Ranvier.

  • This process is called “saltatory conduction”.

Comparison of Unmyelinated and Myelinated Axons

  • Myelinated Axons: Less time required for generation of action potentials compared to Unmyelinated axons

Direction of AP Conduction

  • AP arrives at a node going towards the right, but 'passive' conduction goes both ways.

Peripheral Nervous System (PNS)

PNS contains:

  • Axons and cell bodies of sensory neurons

  • Axons of motor neurons

  • Neurons forming the 'autonomic nervous system'

Generation of APs in Sensory Neurons

  • When a stimulus acts on receptors in sensory neurons, it evokes a graded depolarization known as 'the receptor potential’.

  • The receptor potential spreads passively to the trigger zone, where APs are generated.

  • APs then spread along the axon towards the CNS.

Receptor Potential Details

  • Dependent on stimulus

  • Not voltage-gated (ligand/mechanical)

Coding Stimulus Strength

Information about the strength of the stimulus is coded in the amplitude of the receptor potential and the frequency of APs.