11B - Nervous System - The Action Potential & Synaptic Transmission Notes

Nervous Tissue and Neuroglia

• Building blocks of the nervous system.
• Neurons: Transmit electrical signals rapidly across long distances.
• Neuroglial Cells: Support, insulate, and protect neurons; include astrocytes, Schwann cells, oligodendrocytes, microglia.
• Myelination:
  • Schwann cells (PNS) and oligodendrocytes (CNS) create myelin sheaths for faster transmission.

Nervous System Overview

• Organization:
  • CNS (Central Nervous System): Processing information, decisions.
  • PNS (Peripheral Nervous System): Nerves = bundles of neurons.
  • PNS carries input and outputs between the body and CNS.
• Tissue: Nervous tissue (made up of different cell types).
• Cells:
  • Neurons
  • Neuroglial cells (helper cells)

Types of Neuroglial Cells

• Ependymal Cells:
  • Line the ventricles of the brain and the central canal of the spinal cord.
  • Produce, monitor, and help circulate cerebrospinal fluid (CSF).
• Astrocytes ("star cells"):
  • Maintain the extracellular environment.
  • Regulate nutrient transport.
  • Assist in repairing the brain after injury.
  • Form the blood-brain barrier.
• Schwann Cells:
  • Produce the myelin sheath in the Peripheral Nervous System (PNS).
• Oligodendrocytes:
  • Produce the myelin sheath in the Central Nervous System (CNS).
• Microglia:
  • Act as the brain’s immune defense system.
  • Clear pathogens, dead cells, and debris by phagocytosis.
• Satellite Cells:
  • Surround neuron cell bodies within ganglia in the PNS.
  • Regulate the chemical environment and provide support and nutrients to neurons.

Information Flow and Neuron Structure

• How Neurons Communicate:
  • Dendrites: Receive incoming signals from other neurons.
  • Axon Hillock: Decision point for initiating action potentials based on input summation.
  • Axon and Terminals: Transmit electrical signals away from the soma to the next neuron or effector.
• Functions of the nervous system are determined by connections between neurons.
• Advantage of a neuron having multiple connections with other neurons: More complex functions.
• Each part of a neuron serves a unique role:
  1. Dendrites:
  2. Axon hillock:
  3. Axon:
  4. Axon terminal:
• The action potential always travels in one direction: cell body → axon terminals.
• The action potential is an all-or-nothing event.

Signal Transmission

• Graded potential: Initiated in the pre-synaptic neuron.
• Action potential: Propagated in the axon.
• Neurotransmitter: Released at the axon terminal to signal the post-synaptic neuron.

Neuron Structures and Functions

• Cell body: Integrates incoming signals; houses the nucleus.
• Dendrites: Receives incoming signals from other neurons.
• Axon hillock: Determines whether to initiate an action potential.
• Axon: Conducts the action potential away from the cell body.
• Axon terminal: Releases neurotransmitters to communicate with the next cell.
• Neurotransmitters: Chemicals that transmit signals across a synapse.
• Myelin sheaths: Insulates axons and speeds up signal conduction.

Ion Distribution and Membrane Potential

• The Basis of Neuronal Excitability:
  • Ion Gradients: Higher Na^+ outside the cell, higher K^+ inside the cell.
  • Selective Permeability: Plasma membranes allow differential movement of ions via channels.
  • Electrical Potential Difference: Results in a voltage (mV) across the membrane, typically -70mV at rest.
• Ions move across a membrane to equalize differences in concentration or charge.
• When ion channels are open:
  • Enable specific ions to diffuse across the plasma membrane, moving from areas of higher concentration to areas of lower concentration.
  • Positively charged ions → negatively charged area.
  • Negatively charged ions → positively charged area.
• If an electrode is inserted into a neuron at rest, it will record a negative voltage relative to the outside of the cell (approximately -70 mV).
• There are more negatively charged molecules and ions inside the cell.
• RMP (Resting Membrane Potential) = -70 mV
• Important Note: Anionic proteins (A^-) are present at much higher concentrations inside the cell than outside. These proteins cannot cross the plasma membrane, so they remain trapped inside the cell.
• Extracellular:
  • High Na^+
  • Low K^+
• Intracellular:
  • Low Na^+
  • High K^+
  • High concentration of anionic proteins (negatively charged)

Resting Membrane Potential

• Combination of the following results in the Resting Membrane Potential:
  • Low Na^+ inside the cell
  • Low Cl^- inside the cell
  • High K^+ inside the cell
  • Very high anionic proteins inside the cell
• The membrane of a neuron is full of ion channels.
• What can open an ion channel?
  • Neurotransmitter
  • Changes in voltage

Ion Channels and Their Effects on Membrane Potential

Membrane Potential Definitions

1. Membrane Potential = The difference in electrical potential between the inside and outside of a cell membrane (measured in millivolts, mV).
2. Resting Membrane Potential (RMP) = The membrane potential of a cell "at rest," typically around -70 mV. It is determined by the relative concentrations of negatively and positively charged ions inside and outside the cell.
3. Ion Distribution:
   • Extracellular [Na^+] is higher than intracellular [Na^+].
   • Extracellular [K^+] is lower than intracellular [K^+].
4. Ion Movement:
   • If Na^+ channels open, Na^+ ions would flow into the cell (down the concentration gradient).
   • If K^+ channels open, K^+ ions would flow out of the cell (down the concentration gradient).
5. Voltage-gated ion channels: Open in response to a change in membrane potential (voltage across the membrane).
6. Threshold potential: The specific membrane voltage (typically around -55 mV) at which an action potential is triggered.

Graded Potentials

• Small, Localized Changes in Membrane Potential
• Stimulus-Dependent: Triggered by neurotransmitter binding or sensory stimuli.
• Local Effect: Confined to the region near the stimulus; magnitude varies with strength.
• Depolarization vs. Hyperpolarization: Can make membrane potential more positive (EPSP) or more negative (IPSP).

Neurotransmission and Graded Potentials

1. Neurotransmitter: A chemical that can open a specific channel.
2. Chemically-gated channel: A channel that can be opened by neurotransmitter.
3. Graded potential: A change in membrane potential caused by the opening of an ion channel.

• If Na^+ enters, the positive current flowing in will change the membrane potential to make it less negative (more positive).

Neurotransmission Triggers Graded Potentials

1. Neurotransmitters (“keys”) are released by the axon terminals of the presynaptic neuron and diffuse toward the postsynaptic neuron.
2. NTs bind to receptors (“locks”) on chemically-gated ion channels (“gates”) on the dendrites or cell body of the post-synaptic neuron.
3. Chemically-gated channels open or close in response to NT binding.
4. Ions flow across the membrane, changing the membrane potential.
5. Such changes are called graded potentials.

• Examples of neurotransmitters: Dopamine, Acetylcholine (ACh), Serotonin.
• Important Note: The movement of positive ions leaving the cell (e.g., K^+ efflux) has the same hyperpolarizing effect as negative ions entering the cell (e.g., Cl^- influx).
  • Both result in a more negative charge at the axon hillock.

Ion Channels and Graded Potentials

1. Neurotransmitters bind to ligand-gated ion channels (such as Na^+ channels or K^+ channels) on the postsynaptic membrane.
2. Ion channels open, allowing ions to diffuse into or out of the cell:
   • Example: Na^+ ions diffuse into the cell.
3. The movement of ions causes:
   • A change in membrane potential.
   • A redistribution of ions inside and outside the cell membrane.

• Ions continue to diffuse within the cytoplasm.

1. Some ions eventually reach the axon hillock.
   • At the axon hillock, the membrane potential is evaluated:
     • If the graded potential is large enough (i.e., reaches threshold potential), an action potential is triggered.

Summation of Graded Potentials

• Each neuron may receive inputs from one, a few, or thousands of other neurons.
• Many graded potentials can arrive at the same time.
• It is the sum of all incoming graded potentials that determines whether an action potential is triggered.

Spatial and Temporal Summation

• Graded potentials are ‘added up’ at the axon hillock (spatial and temporal summation).
• If the membrane potential reaches a certain threshold value, an action potential is initiated.
  • Spatial summation: GPs occurring simultaneously at several locations.
  • Temporal summation: Several GPs in short sequence at the same location.

1. Graded potentials may be:
   • Excitatory (EPSPs): Excitatory postsynaptic potentials → make an AP more likely.
   • Inhibitory (IPSPs): Inhibitory postsynaptic potentials → make an AP less likely.
2. For each of the following chemically-gated ion channels, indicate whether opening will result in an excitatory (E) or inhibitory (I) graded potential.
   • Na^+ channel (higher extracellular [Na^+]): E
   • Cl^- channel? (higher extracellular [Cl^-]): I
   • K^+ channel? (higher intracellular [K^+]): I

Graded Potential Calculations

5.1. Resting Membrane Potential = -70mV; threshold: -50mV; GPs: +10mV, -5mV, +20mV, -6mV: No action potential will be generated, since the sum is -70 + 10 - 5 + 20 -6 = -51 mV which is less than the threshold of -50mV

5.2. Resting Membrane Potential = -80mV; threshold: -60mV; GPs: +30mV, +11mV, -20mV: Action potential will be generated. The sum is -80 + 30 + 11 - 20 = -59 mV which is greater than the threshold of -60mV

5.3. Resting Membrane Potential = -70mV; threshold: -55mV; GPs: +30mV, +20mV, -12mV: Action potential will be generated. The sum is -70 + 30 + 20 - 12 = -32 mV which is greater than the threshold of -55mV

Intensity Encoding and Threshold Potentials

• Intensity is encoded by frequency of APs in a given amount of time.
• Different types of cells have different threshold potentials, e.g.:
  • Ear neurons
  • Pressure receptors

Location of Channels and Potentials on a Neuron

• Ligand (chemically)-gated channels: Dendrites, cell body
• Voltage-gated channels: Axon hillock, axon
• Graded potentials: Dendrites, cell body
• Action potentials: Axon

Functions of Chemically-Gated and Voltage-Gated Channels

• Chemically-gated channels:
  • Locations: Dendrites, cell body
  • Opened/Activated by: Neurotransmitters (ligands)
  • Associated with: Graded potentials
• Voltage-gated channels:
  • Locations: Axon hillock, axon
  • Opened/Activated by: Changes in membrane potential (voltage)
  • Associated with: Action potentials

The Action Potential

• An action potential is initiated if the graded potential that reaches the axon hillock is large enough to reach the threshold potential.
• At threshold, voltage-gated Na^+ channels open, triggering the action potential.
• Note: Different types of neurons have different threshold potentials.
• Example: Stimulus Types That Cause Graded Potentials (Trigger Na^+ Entry)
  • Physical: touch, pressure, movement (mechanoreceptors).
  • Chemical: neurotransmitters (chemoreceptors/ligand-gated channels).
  • Light: activates photoreceptors.
  • Electrical charge: voltage-gated channels (electroreceptors).
  • Temperature: thermoreceptors (heat/cold).
  • Pain: nociceptors respond to excess stimulation.

Depolarization

• Voltage-gated Na^+ channels open → Na^+ ions rush into the neuron.
• This triggers nearby Na^+ channels to open.
• Membrane potential rapidly rises to about +30 mV.
• Na^+ channels close at around +30 mV to stop further Na^+ influx.
• At +30 mV, voltage-gated K^+ channels open to begin repolarization.

Repolarization

• Voltage-gated K^+ channels open at +30 mV → K^+ ions rush out of the cell.
• Membrane potential decreases rapidly (repolarization).
• Around -55 mV, K^+ channels begin to close to prevent further K^+ loss.
• K^+ channels close slowly, causing hyperpolarization (membrane becomes more negative than resting potential).
  • Na⁺ and K⁺ ions are now in the wrong places!
  • Solution: ➔ Na^+/K^+ ATPase pump restores resting ion balance (uses ATP).

Hyperpolarization and Return to Resting State

• Na^+/K^+ pumps restore ion concentrations after an action potential.
• This pump uses ~30% of all the ATP produced by the body!
• Restores the Resting Membrane Potential (RMP) to about -70 mV.
• Once RMP is restored, a new action potential can be generated.
• Refractory period =
  • Time between Na^+ channel closure (+30 mV) and channel readiness to reopen.
  • No Na^+ influx during this time.
  • No new action potential can be initiated until recovery.

Propagation of Action Potentials

0. If threshold membrane potential is reached at axon hillock:
1. Voltage-gated Na^+ channels at the axon hillock change shape and open.
2. Na^+ diffuses into the cell (depolarization)
3. Na^+ ions diffuse further within the cell → threshold membrane is reached at adjacent locations…
   • Adjacent voltage-gated Na^+ channels open.
   • Na^+ diffuses into cell
   • As more Na^+ ions diffuse towards nearby Na^+ channels, threshold is achieved and further Na^+ channels are opened.
   • Steps 1,2,3 are repeated until the action potential reaches axon terminals.
4. As membrane potential reaches another threshold value (+30mv):
   • Na^+ channels close, ending depolarization.
   • K^+ channels open, initiating repolarization.
5. Ion concentrations are restored via action of the Na^+/K^+ pump, requiring lots of energy!

Clinical Relevance: Multiple Sclerosis

• Autoimmune Attack: The immune system attacks and destroys myelin in the CNS.
• Consequences: Impaired signal conduction leads to sensory, motor, and cognitive symptoms.
• Variability in Symptoms: Depends on which neurons are affected and extent of demyelination.

Myelin Sheaths

• Formed by:
  • Schwann cells (Peripheral Nervous System - PNS)
  • Oligodendrocytes (Central Nervous System - CNS)
• Made of phospholipid-rich membranes → gives rise to white matter.
• Functions:
  • Insulate and protect axons
  • Speed up signal transmission (saltatory conduction)
• Nodes of Ranvier
  • Gaps between myelin sheaths
  • Only locations with voltage-gated ion channels
  • Enable faster conduction by allowing APs to "jump" node-to-node

Multiple Sclerosis Pathology

1. Auto-immune disease: Immune system attacks and destroys myelin
2. Consequences? Impaired signal conduction
3. Why do signs and symptoms of multiple sclerosis vary between patients?
   • Different levels of demyelination
   • Different neurons with different functions affected
4. How may neurons attempt to restore normal function? Neurons may attempt to remyelinate, although this is not always successful.

Nervous System Excitability & Transmission — Quick Summary

• Nervous System:
  • CNS: Integration and decision-making.
  • PNS: Sensory and motor relay.
• Neurons and Neuroglia
• Membrane Potentials: RMP ~-70mV; Na^+/K^+ gradients drive excitability.
• Graded & Action Potentials: Local graded changes can trigger full action potentials at threshold.
• Propagation & Myelination: Myelinated axons allow faster, more efficient signal conduction.
• Clinical Insight: Multiple sclerosis results from autoimmune demyelination.