Nerve Impulse Transmission - Comprehensive Study Guide

1. Overview of Neural Communication

Nerve impulse transmission is the fundamental mechanism by which neurons communicate information throughout the nervous system. This process involves electrical and chemical signals that allow rapid information transfer across long distances in the body.

2. Resting Membrane Potential

Establishment and Maintenance

• Resting potential: -70 mV (typical range: -65 to -75 mV)
• Maintained by the sodium-potassium pump (Na⁺/K⁺-ATPase)
• Pump ratio: 3 Na⁺ out : 2 K⁺ in per ATP molecule
• Creates net negative charge inside the cell

Ion Distribution at Rest

• Intracellular fluid: High K⁺ (~140 mM), Low Na⁺ (~10 mM)
• Extracellular fluid: High Na⁺ (~145 mM), Low K⁺ (~5 mM)
• Membrane permeability at rest: K⁺ > Cl⁻ >> Na⁺

3. Action Potential Generation

Threshold Potential

• Threshold value: -55 mV (approximately)
• Critical membrane potential that must be reached to trigger an action potential
• Represents the point where voltage-gated Na⁺ channels begin rapid opening

All-or-Nothing Principle

• Action potentials either occur completely or not at all
• No gradation in amplitude once threshold is reached
• Amplitude remains constant (~100 mV swing from -70 to +30 mV)
• Duration: ~1-2 milliseconds in most neurons

4. Phases of Action Potential

Phase 1: Depolarization (-70 mV to +30 mV)

• Initial trigger: Stimulus reaches threshold (-55 mV)
• Mechanism: Rapid opening of voltage-gated Na⁺ channels
• Na⁺ influx: Massive inward current of sodium ions
• Peak potential: +30 mV to +40 mV
• Time course: ~0.5-1.0 milliseconds

Phase 2: Repolarization (+30 mV to -70 mV)

• Mechanism:
  • Voltage-gated Na⁺ channels inactivate
  • Voltage-gated K⁺ channels open
• K⁺ efflux: Potassium ions flow out of the cell
• Duration: ~1-2 milliseconds
• Result: Membrane potential returns toward resting level

Phase 3: Hyperpolarization (-70 mV to -80 mV)

• Cause: Delayed closure of voltage-gated K⁺ channels
• Potential: Can reach -80 to -90 mV
• Duration: 2-4 milliseconds
• Recovery: Na⁺/K⁺ pump restores resting potential

5. Refractory Periods

Absolute Refractory Period

• Duration: 1-2 milliseconds
• Mechanism: Na⁺ channels are inactivated
• Characteristic: No stimulus, regardless of strength, can trigger another action potential
• Functional significance: Ensures unidirectional propagation

Relative Refractory Period

• Duration: 2-4 milliseconds (following absolute period)
• Mechanism: Some Na⁺ channels recovered, K⁺ channels still open
• Characteristic: Stronger-than-normal stimulus required
• Threshold: Elevated to -50 to -45 mV during this period

6. Roles of Sodium (Na⁺) and Potassium (K⁺)

Sodium (Na⁺)

• Primary role: Depolarization phase
• Channel types:
  • Voltage-gated Na⁺ channels (action potential generation)
  • Leak channels (minor contribution to resting potential)
• Activation: Rapid opening at threshold
• Inactivation: Automatic closure during peak potential
• Driving force: Large electrochemical gradient favors influx

Potassium (K⁺)

• Primary roles:
  • Maintaining resting potential
  • Repolarization phase
• Channel types:
  • Voltage-gated K⁺ channels (delayed opening)
  • Leak channels (major contributor to resting potential)
• Characteristics: Slower kinetics than Na⁺ channels
• Driving force: Electrochemical gradient favors efflux during action potential

7. Saltatory Conduction

Myelinated Axons

• Myelin sheath: Insulating layers of lipid-rich membrane
• Formation:
  • CNS: Oligodendrocytes
  • PNS: Schwann cells
• Nodes of Ranvier: Unmyelinated gaps (~1 μm wide, 1-2 mm apart)

Mechanism of Saltatory Conduction

• Current flow: Occurs only at nodes of Ranvier
• "Jumping": Action potential appears to jump from node to node
• Speed advantage:
  • Myelinated axons: 1-120 m/s
  • Unmyelinated axons: 0.5-2 m/s
• Energy efficiency: Reduced metabolic cost

Factors Affecting Conduction Velocity

• Axon diameter: Larger diameter = faster conduction
• Myelination: Presence increases speed dramatically
• Temperature: Higher temperature = faster conduction
• Ion channel density: Higher density at nodes = faster conduction

8. Synaptic Transmission

Synaptic Structure

• Presynaptic terminal: Contains synaptic vesicles and Ca²⁺ channels
• Synaptic cleft: ~20-50 nm gap between neurons
• Postsynaptic membrane: Contains neurotransmitter receptors

Chemical Synaptic Transmission Process

Step 1: Action Potential Arrival

• Depolarization reaches presynaptic terminal
• Voltage-gated Ca²⁺ channels open

Step 2: Calcium Influx

• Ca²⁺ concentration increases from ~0.1 μM to ~10-100 μM
• Triggers vesicle fusion machinery

Step 3: Vesicle Fusion and Exocytosis

• SNARE proteins: Mediate vesicle-membrane fusion
• Synaptotagmin: Ca²⁺ sensor protein
• Release: ~1000-5000 neurotransmitter molecules per vesicle

Step 4: Neurotransmitter Diffusion

• Molecules cross synaptic cleft
• Time: ~0.1-0.5 milliseconds

Step 5: Receptor Binding

• Neurotransmitter binds to postsynaptic receptors
• Conformational change opens ion channels

Synaptic Delay

• Total delay: 0.5-1.0 milliseconds
• Components:
  • Ca²⁺ influx and binding: ~0.2 ms
  • Vesicle fusion: ~0.2 ms
  • Neurotransmitter diffusion: ~0.1 ms
  • Receptor activation: ~0.2 ms

9. Neurotransmitter Receptors

Ionotropic Receptors (Ligand-gated ion channels)

• Structure: Receptor and ion channel are same protein
• Response time: 1-5 milliseconds
• Duration: 10-100 milliseconds
• Examples:
  • Nicotinic acetylcholine receptors (Na⁺/K⁺)
  • GABA-A receptors (Cl⁻)
  • NMDA and AMPA glutamate receptors

Metabotropic Receptors (G-protein coupled)

• Structure: Receptor activates intracellular signaling cascades
• Response time: 50-500 milliseconds
• Duration: Seconds to minutes
• Examples:
  • Muscarinic acetylcholine receptors
  • Dopamine receptors
  • Serotonin receptors

10. Postsynaptic Potentials

Excitatory Postsynaptic Potentials (EPSPs)

• Mechanism: Opening of Na⁺/K⁺ channels
• Effect: Depolarization (typically 1-5 mV)
• Duration: 10-50 milliseconds
• Neurotransmitters: Glutamate, acetylcholine (nicotinic)

Inhibitory Postsynaptic Potentials (IPSPs)

• Mechanism: Opening of Cl⁻ or K⁺ channels
• Effect: Hyperpolarization or stabilization at rest
• Amplitude: 1-5 mV (in hyperpolarizing direction)
• Neurotransmitters: GABA, glycine

Summation

• Temporal summation: Multiple signals from same synapse
• Spatial summation: Signals from multiple synapses
• Integration: Determines whether threshold is reached

11. Neurotransmitter Removal

Mechanisms

1. Enzymatic degradation

   • Example: Acetylcholinesterase breaks down acetylcholine
   • Time course: Milliseconds

2. Reuptake

   • Transporter proteins remove neurotransmitter
   • Examples: Dopamine, serotonin, norepinephrine transporters

3. Diffusion

   • Neurotransmitter moves away from synaptic cleft
   • Slower process, minutes to hours

12. Factors Affecting Synaptic Transmission

Presynaptic Factors

• Ca²⁺ concentration: Higher = more transmitter release
• Vesicle availability: Determines sustained transmission
• Previous activity: Can cause facilitation or depression

Postsynaptic Factors

• Receptor density: More receptors = stronger response
• Receptor sensitivity: Can be modified by drugs or disease
• Membrane potential: Affects driving force for ions

Environmental Factors

• Temperature: Affects enzyme activity and diffusion
• pH: Alters protein conformation and function
• Ion concentrations: Particularly Ca²⁺, Mg²⁺, and K⁺

13. Clinical Significance

Neurological Disorders

• Multiple Sclerosis: Demyelination slows conduction
• Myasthenia Gravis: Autoimmune attack on acetylcholine receptors
• Epilepsy: Abnormal synchronous firing of neurons

Pharmacological Targets

• Local anesthetics: Block voltage-gated Na⁺ channels
• Anticonvulsants: Modulate Na⁺ or Ca²⁺ channels
• Antidepressants: Block neurotransmitter reuptake

14. Key Numerical Values Summary

15. Conclusion

Nerve impulse transmission represents one of the most elegant and efficient communication systems in biology. The precise coordination of ion movements, voltage changes, and chemical signaling allows for rapid, reliable information transfer throughout the nervous system. Understanding these mechanisms is crucial for comprehending both normal neural function and the pathophysiology of neurological disorders.