Neurophysiology of Nerve Impulses

Electrical Potentials and Currents

• A nerve pathway is not a continuous "wire" but rather a series of separate cells.
• Neuronal communication is based on mechanisms for producing electrical potentials and currents.
  • Electrical Potential: Difference in concentration of charged particles between different parts of the cell.
  • Electrical Current: Flow of charged particles from one point to another within the cell.

Structure of Neurons

• Neurons (nerve cells) are specialized cells that conduct messages in the form of electrical impulses throughout the body.
• Neurons consist of:
  • Cell body (soma or perikaryon)
  • Axon
  • Dendrites
• Each neuron has a single axon that generates and conducts nerve impulses away from the cell body to the axon terminals.

Structural Components of a Neuron

• Dendrites: Receive signals from other neurons.
• Cell Body (Soma or Perikaryon):
  • Contains nucleus and other organelles.
  • Nissl bodies (RER and free ribosomes).
• Axon:
  • Arises from the axon hillock.
  • Initial segment of axon.
  • Axolemma: Plasma membrane of the axon.
  • Telodendria: Terminal branches of the axon.
• Synaptic Terminals: Ends of telodendria where communication occurs with other neurons or cells.

Transmembrane Potential

• The interior (cytoplasmic side) of the plasma membrane is slightly negative relative to the outside (extracellular fluid side).
  • Transmembrane Potential: The unequal charge across the plasma membrane.
  • Due to differences in the permeability of the membrane to various ions.
  • Resting Potential: The transmembrane potential in an undisturbed cell.
  • Only leakage channels for Na^+ and K^+ are open.
  • All gated Na^+ and K^+ channels are closed.
• The average resting membrane potential varies by cell type but averages -70 mV.

Ion Distribution

• Extracellular Fluid:
  • High concentration of Na^+ and Cl^-.
• Cytosol:
  • High concentration of K^+ and negatively charged proteins.
• Negatively charged proteins inside the cell cannot cross the cell membrane.
• K^+ diffuses out of the cell through K^+ leakage channels, down its concentration gradient, more easily than Na^+ enters the cell through Na^+ leakage channels.
• The inner plasma membrane surface has an excess of negative charges relative to the outer surface.

Resting Membrane Potential Explanation

• Plasma membrane is very permeable to K^+.
  • K^+ leaks out until the electrical gradient created attracts it back in.
• Cytoplasmic anions cannot escape due to size or charge (PO4^{2-}, SO4^{2-}, organic acids, proteins).
• Plasma membrane is much less permeable to Na^+.
• Na^+/K^+ Pumps:
  • Pump out 3 Na^+ for every 2 K^+ they bring in.
  • Work continuously and require a great deal of ATP.
  • Necessitate glucose and oxygen supply to nerve tissue.

Transmembrane Channels

• Membrane Channels: Control the movement of ions across the plasma membrane.
  • Na^+ and K^+ are primary determinants of the transmembrane potential of neurons and many other cell types.
• Two main types of membrane channels:
  • Leak Channels (passive)
  • Gated Channels (active)
  • Chemically Gated (ligand-gated)
  • Voltage Gated
  • Mechanically Gated

Leak Channels (Passive)

• Non-gated, always open.
• Permeability can vary based on local conditions.
• Important in establishing resting membrane potential.

Gated Channels (Active)

• Open and close in response to specific stimuli.
  • Chemically Gated (ligand-gated) Channels:
  • Open/close when they bind specific chemicals (i.e., neurotransmitters).
  • Most abundant on dendrites and cell body of a neuron.
  • Voltage-Gated Channels:
  • Open and close in response to changes in membrane potential.
  • Participate in the generation and conduction of action potentials.
  • Found in neural axons, skeletal muscle sarcolemma, and cardiac muscle.
  • Mechanically Gated Channels:
  • Open and close in response to physical deformation of receptors (i.e., touch, pressure, vibration).
  • The force distorts the channel, causing the gates to open.

Resting Membrane Potential Changes

• Depolarization and hyperpolarization are changes in the resting membrane potential.

Depolarization

• Any shift from the resting membrane potential toward a more positive potential.
• Occurs when the resting membrane is exposed to a stimulus that opens the Na^+ chemical channels.
  • Na^+ enters the cell.
• The positive charge of Na^+ shifts the transmembrane potential toward 0 mV.
  • This is called depolarization.

Magnitude of Depolarization

• The maximum change in transmembrane potential is proportional to the size of the stimulus.
  • The greater the stimulus:
  • The greater the number of chemical channels that open.
  • The more Na^+ that enters the cell.
  • The greater the membrane area affected.
  • The greater the degree of depolarization.

Transmembrane Potential Changes: Types of Electrical Signals

• Changes in membrane potential can produce two types of signals:
  • Graded Potentials
  • Action Potentials

Graded Potentials

• Also called local potentials.
• A short-lived localized change in the resting membrane potential.
• Changes in the transmembrane potential that cannot spread far from the site of stimulation.
  • These changes cause current flows that decrease in magnitude with distance.
• Magnitude varies with the strength of the stimulus.
  • The greater the stimulus, the greater the voltage change and the farther the current will flow.
• Any stimulus that opens a chemical-gated channel will produce a graded potential.

Action Potential

• A brief reversal of the membrane potential.
• Propagated changes in the transmembrane potential that, once initiated, affect the entire excitable membrane.
• An electrical impulse that travels along the cell membrane and does not diminish as it moves away from its source.
• For an action potential to occur:
  • Depolarization has to be great enough to reach the membrane threshold, causing the voltage-gated channels to open.
  • Threshold: The minimum voltage to stimulate an action potential.
  • Varies, but average is about -55mV in many neurons.
• Only cells with excitable membranes (neurons and muscle cells) can generate action potentials.

Action Potentials Characteristics

• The principle way neurons communicate
• Follow the all-or-none principle.
  • A stimulus either triggers an action potential or does not produce one at all.
  • You cannot have a partial action potential.
  • If the threshold is reached, an action potential will occur.
• Irreversible.
  • Once started, goes to completion and cannot be stopped.
• The impulse generated will travel the entire length of the membrane.
• Nondecremental.
  • Does not get weaker with distance.

Action Potential - Generation Involves

• Depolarization
• Repolarization
• Hyperpolarization
• Only neurons and muscle cells generate action potentials

Generation of an Action Potential - Depolarization

• A stimulus that opens the chemical-gated channels.
  • The stimulus must cause a depolarization large enough to open voltage-gated Na^+ channels to initiate an action potential.
  • A more dramatic change in the membrane potential is produced where there is a high density of voltage-gated channels.
  • Trigger zone has 500 channels/mm^2 (normal is 75).
• If the stimulus is great enough to cause the plasma membrane potential to reach the threshold potential (-55mV):
  • Voltage-gated Na^+ channels open.
  • Na^+ rushes into the cell, generating an action potential.
• Not all depolarizations lead to action potentials.
  • The stimulus must be significant enough to cause the membrane potential to reach the threshold.

Depolarization Details

• When the voltage-gated Na^+ channels open, the plasma membrane becomes much more permeable to Na^+.
• Due to their electrochemical gradient, Na^+ rushes in, and rapid depolarization occurs.
• The inner membrane surface now contains more + ions than - ions.
• The transmembrane potential changes from -70 mV to a positive value.

Generation of an Action Potential - Repolarization

• The process that occurs when the stimulus is removed, and the transmembrane potential begins to return to normal resting levels.
• Is the re-establishment of the resting membrane potential.
• As the membrane potential approaches +30mV:
  • Repolarization begins
  • Voltage-gated Na^+ channels begin to close.
  • Voltage-gated K^+ channels open.
  • K^+ exits the cell
  • K^+ flows out, down the electrochemical gradient.
  • The transmembrane potential shifts back towards its resting level.
  • Voltage-gated K^+ channels begin closing as the membrane potential approaches the normal resting potential (-70 mV).
  • It takes time for all of the voltage-gated K^+ channels to close.
  • Therefore, the membrane potential passes the resting state (-70mV) and produces hyperpolarization.

Hyperpolarization

• K^+ continues to exit the cell until all of the voltage-gated K^+ channels close.
  • They are closed at about -90 mV.
• The leak channels and Na^+/K^+ pumps help to restore the plasma membrane to its resting membrane potential (-70mV).

Action Potential Summary

• Resting membrane potential: -70mV
• Threshold: -55mV
• Peak of action potential: +30mV
• Hyperpolarization: -90mV

The Refractory Period

• The time period from which an action potential begins until the normal resting potential has stabilized.
• During this period, the membrane will not respond normally to additional depolarizing stimuli.
• Represents a period of resistance to stimulation.
• Consists of 2 parts:
  • Absolute Refractory Period:
  • As long as the voltage-gated Na^+ channels are open, no stimulus will trigger an action potential.
  • Relative Refractory Period:
  • As long as the voltage-gated K^+ channels are open, only an especially strong stimulus will trigger a new action potential.
• The refractory period occurs only to a small segment of the plasma membrane at one time and quickly recovers.

Myelin Sheath

• A whitish, protein-lipid substance made by:
  • Oligodendrocytes in the CNS
  • Schwann cells in the PNS
• Protects and electrically insulates an axon.
  • Myelinated Internode: The area of the axon wrapped in myelin.
  • Nodes of Ranvier: Small gaps between the myelinated internodes.
• Myelin Sheaths are only associated with axons, not dendrites.
  • White Matter: Consists of regions of CNS with many myelinated nerves.
  • Gray matter: Consists of unmyelinated areas of CNS (short axons).

Propagation of Action Potentials

• Action Potentials spread (propagate) along the surface of the axon membrane.
• Travel along an axon by:
  • Continuous Propagation (unmyelinated axons)
  • Saltatory Propagation (myelinated axons)

Continuous Propagation (Unmyelinated Axons)

• The action potential moves along the axon membrane in segments, starting at the initial segment of the axon.
• The local current spreads in all directions.
• As the next segment depolarizes and an action potential is generated, the previous segment enters the refractory period.
  • Therefore, the action potential can only move in one direction (forward).
• The axon hillock cannot respond with an action potential because it lacks voltage-gated Na^+ channels.
• The action potential moves across the surface of the membrane in a series of tiny steps.

Saltatory Propagation (Myelinated Axons)

• Myelin increases resistance to the flow of ions across the membrane.
• Ions can only cross the plasma membrane at the nodes of Ranvier.
  • When an action potential is generated in a myelinated fiber:
  • The local depolarizing current does not dissipate through the adjacent membrane regions, which are nonexcitable.
  • Instead, the current is maintained and moves rapidly to the next node of Ranvier, where it triggers another action potential.
  • Action potentials are triggered only at the nodes of Ranvier.
• In saltatory conduction, the impulse jumps from node to node along the axon.
• Nerve impulses are carried along myelinated axons (saltatory propagation) faster than in unmyelinated axons (continuous propagation).

Speed of Impulse Propagation

• Speed of nerve impulse transmission is affected by:
  • Myelin
  • Diameter of Axon
  • The larger the diameter, the lower the resistance, the faster the propagation speed.
  • Because the cytosol offers less resistance than the plasma membrane.
• Speeds
  • Small, unmyelinated fibers = 0.5 - 2.0 m/sec
  • Small, myelinated fibers = 3 - 15.0 m/sec
  • Large, myelinated fibers = up to 120 m/sec
• Functions
  • Slow signals supply the stomach and dilate the pupil.
  • Fast signals supply skeletal muscles and transport sensory signals for vision and balance.