Fundamentals of the Nervous System and Nervous Tissue

Membrane Potentials

• Neurons, like all cells, have a resting membrane potential.
• Neurons, unlike most cells, can rapidly change their resting membrane potential.
• Neurons are highly excitable.

Basic Principles of Electricity

• Opposite charges are attracted to each other.
• Energy is required to keep opposite charges separated across a membrane.
• Energy is liberated when charges move toward one another.
• When opposite charges are separated, the system has potential energy.
• Voltage: A measure of potential energy generated by separated charge, measured between two points in volts (V) or millivolts (mV). Also called potential difference or potential.
• Charge difference across the plasma membrane results in potential.
• A greater charge difference between points means a higher voltage.
• Current: Flow of electrical charge (ions) between two points.
• Current can be used to do work and is dependent on voltage and resistance.
• Resistance: Hindrance to charge flow.
  • Insulator: A substance with high electrical resistance.
  • Conductor: A substance with low electrical resistance.
• Ohm’s Law: Current (I) = \frac{Voltage (V)}{Resistance (R)}
  • Current is directly proportional to voltage: the greater the voltage, the greater the current.
  • No net current flow occurs between points with the same potential.
  • Current is inversely proportional to resistance: the greater the resistance, the smaller the current.

Role of Membrane Ion Channels

• Large proteins serve as selective membrane ion channels (e.g., a K^+ ion channel allows only K^+ to pass through).
• Two main types of ion channels:
  • Leakage (nongated) channels: Always open.
  • Gated channels: Part of the protein changes shape to open/close the channel.
• Three main gated channels:
  • Chemically gated.
  • Voltage-gated.
  • Mechanically gated.
• Chemically gated (ligand-gated) channels: Open only with the binding of a specific chemical (e.g., neurotransmitter).
• Voltage-gated channels: Open and close in response to changes in membrane potential.
• Mechanically gated channels: Open and close in response to physical deformation of receptors (e.g., sensory receptors).
• When gated channels are open, ions diffuse quickly:
  • Along chemical concentration gradients (from higher to lower concentration).
  • Along electrical gradients (toward opposite electrical charge).
• Electrochemical gradient: Electrical and chemical gradients combined.
• Ion flow creates an electrical current and voltage changes across the membrane.
  • Expressed by rearranged Ohm’s law equation: V = IR

Generating the Resting Membrane Potential

• A voltmeter can measure the potential (charge) difference across the membrane of a resting cell.
• The resting membrane potential of a resting neuron is approximately -70 mV.
  • The cytoplasmic side of the membrane is negatively charged relative to the outside.
  • The actual voltage difference varies from -40 mV to -90 mV.
  • The membrane is said to be polarized.
• Potential is generated by:
  • Differences in ionic composition of intracellular fluid (ICF) and extracellular fluid (ECF).
  • Differences in plasma membrane permeability.
• Differences in ionic composition:
  • ECF has a higher concentration of Na^+ than ICF, balanced chiefly by chloride ions (Cl^−).
  • ICF has a higher concentration of K^+ than ECF, balanced by negatively charged proteins.
  • K^+ plays the most important role in membrane potential.
• Differences in plasma membrane permeability:
  • Impermeable to large anionic proteins.
  • Slightly permeable to Na^+ (through leakage channels); sodium diffuses into the cell down its concentration gradient.
  • 25 times more permeable to K^+ than sodium (more leakage channels); potassium diffuses out of the cell down its concentration gradient.
  • Quite permeable to Cl^−.
• More potassium diffuses out than sodium diffuses in, so the inside of the cell is more negative, establishing the resting membrane potential.
• The sodium-potassium pump (Na^+/K^+ ATPase) stabilizes the resting membrane potential.
  • Maintains concentration gradients for Na^+ and K^+.
  • Three Na^+ are pumped out of the cell while two K^+ are pumped back in.

Changing the Resting Membrane Potential

• Membrane potential changes when:
  • Concentrations of ions across the membrane change.
  • Membrane permeability to ions changes.
• Changes produce two types of signals:
  • Graded potentials: Incoming signals operating over short distances.
  • Action potentials: Long-distance signals of axons.
• Changes in membrane potential are used as signals to receive, integrate, and send information.
• Terms describing membrane potential changes relative to resting membrane potential:
  • Depolarization: Decrease in membrane potential (moves toward zero and above).
    • The inside of the membrane becomes less negative than the resting membrane potential.
    • The probability of producing an impulse increases.
  • Hyperpolarization: Increase in membrane potential (moves away from zero).
    • The inside of the membrane becomes more negative than the resting membrane potential.
    • The probability of producing an impulse decreases.

Graded Potentials

• Short-lived, localized changes in membrane potential.
  • The stronger the stimulus, the more the voltage changes and the farther the current flows.
• Triggered by a stimulus that opens gated ion channels, resulting in depolarization or sometimes hyperpolarization.
• Named according to location and function:
  • Receptor potential (generator potential): Graded potentials in receptors of sensory neurons.
  • Postsynaptic potential: Neuron graded potential.
• Once a gated ion channel opens, depolarization spreads from one area of the membrane to the next.
• Current flows but dissipates quickly and decays.
• Graded potentials are signals only over short distances.

Action Potentials

• The principal way neurons send signals and a means of long-distance neural communication.
• Occur only in muscle cells and axons of neurons.
• Brief reversal of membrane potential with a change in voltage of ~100 mV.
• Action potentials (APs) do not decay over distance as graded potentials do.
• In neurons, also referred to as a nerve impulse.
• Involves the opening of specific voltage-gated channels.
• Four main steps:
  • Resting state: All gated Na^+ and K^+ channels are closed.
    • Only leakage channels for Na^+ and K^+ are open, maintaining the resting membrane potential.
    • Each Na^+ channel has two voltage-sensitive gates:
      • Activation gates: closed at rest; open with depolarization, allowing Na^+ to enter the cell.
      • Inactivation gates: open at rest; block the channel once it's open to prevent more Na^+ from entering the cell.
    • Each K^+ channel has one voltage-sensitive gate:
      • Closed at rest.
      • Opens slowly with depolarization.
  • Depolarization: Na^+ channels open.
    • Depolarizing local currents open voltage-gated Na^+ channels, and Na^+ rushes into the cell.
    • Na^+ activation and inactivation gates open.
    • Na^+ influx causes more depolarization, which opens more Na^+ channels.
    • As a result, ICF becomes less negative.
    • At threshold (-55 to -50 mV), positive feedback causes the opening of all Na^+ channels, resulting in a large action potential spike.
    • Membrane polarity jumps to +30 mV.
  • Repolarization: Na^+ channels are inactivating, and K^+ channels open.
    • Na^+ channel inactivation gates close.
    • Membrane permeability to Na^+ declines to resting state, and the AP spike stops rising.
    • Voltage-gated K^+ channels open.
    • K^+ exits the cell down its electrochemical gradient.
    • Repolarization: the membrane returns to resting membrane potential.
  • Hyperpolarization: Some K^+ channels remain open, and Na^+ channels reset.
    • Some K^+ channels remain open, allowing excessive K^+ efflux, making the inside of the membrane more negative than in the resting state.
    • This causes hyperpolarization of the membrane (slight dip below resting voltage).
    • Na^+ channels also begin to reset.
• Repolarization resets electrical conditions, not ionic conditions.
• After repolarization, Na^+/K^+ pumps (thousands in an axon) restore ionic conditions.

Threshold and the All-or-None Phenomenon

• Not all depolarization events produce APs.
• For an axon to “fire,” depolarization must reach the threshold voltage to trigger an AP.
• At threshold:
  • The membrane is depolarized by 15 to 20 mV.
  • Na^+ permeability increases.
  • Na^+ influx exceeds K^+ efflux.
  • The positive feedback cycle begins.
• All-or-None: An AP either happens completely or does not happen at all.

Propagation of an Action Potential

• Propagation allows an AP to be transmitted from its origin down the entire axon length toward the terminals.
• Na^+ influx through voltage gates in one membrane area causes local currents that cause the opening of Na^+ voltage gates in adjacent membrane areas.
  • Leads to depolarization of that area, which in turn causes depolarization in the next area.
• Once initiated, an AP is self-propagating.
  • In nonmyelinated axons, each successive segment of the membrane depolarizes, then repolarizes.
  • Propagation in myelinated axons differs.
• Since Na^+ channels closer to the AP origin are still inactivated, no new AP is generated there.
• The AP occurs only in a forward direction.

Coding for Stimulus Intensity

• All action potentials are alike and independent of stimulus intensity.
• The CNS tells the difference between a weak stimulus and a strong one by the frequency of impulses.
  • Frequency is the number of impulses (APs) received per second.
  • Higher frequencies mean a stronger stimulus.

Refractory Periods

• Refractory period: the time in which a neuron cannot trigger another AP.
  • Voltage-gated Na^+ channels are open, so the neuron cannot respond to another stimulus.
• Two types:
  • Absolute refractory period: Time from the opening of Na^+ channels until the resetting of the channels.
    • Ensures that each AP is an all-or-none event.
    • Enforces one-way transmission of nerve impulses.
  • Relative refractory period: Follows the absolute refractory period.
    • Most Na^+ channels have returned to their resting state.
    • Some K^+ channels are still open; repolarization is occurring.
    • The threshold for AP generation is elevated; only an exceptionally strong stimulus could stimulate an AP.

Conduction Velocity

• APs occur only in axons, not other cell areas.
• AP conduction velocities in axons vary widely.
• The rate of AP propagation depends on two factors:
  • Axon diameter: Larger-diameter fibers have less resistance to local current flow, so they have faster impulse conduction.
  • Degree of myelination: Two types of conduction, depending on the presence or absence of myelin:
    • Continuous conduction.
    • Saltatory conduction.
  • Continuous conduction: Slow conduction that occurs in nonmyelinated axons.
  • Saltatory conduction: Occurs only in myelinated axons and is about 30 times faster.
    • Myelin sheaths insulate and prevent leakage of charge.
    • Voltage-gated Na^+ channels are located at myelin sheath gaps.
    • APs are generated only at the gaps.
    • The electrical signal appears to “jump” rapidly from gap to gap.

Clinical Imbalance: Multiple Sclerosis (MS)

• MS is an autoimmune disease that affects primarily young adults.
• Myelin sheaths in the CNS are destroyed when the immune system attacks myelin, turning myelin into hardened lesions called scleroses.
  • Impulse conduction slows and eventually ceases.
  • Demyelinated axons increase Na^+ channels, causing cycles of relapse and remission.
• Symptoms include visual disturbances, weakness, loss of muscular control, speech disturbances, incontinence.
• Treatment involves drugs that modify immune system activity.
• Maintaining high blood levels of vitamin D may reduce the risk of development.

Nerve Fiber Classification

• Nerve fibers are classified according to diameter, degree of myelination, and speed of conduction, falling into three groups:
  • Group A fibers: Largest diameter, myelinated somatic sensory and motor fibers of skin, skeletal muscles, and joints; transmit at 150 m/s (~300 mph).
  • Group B fibers: Intermediate diameter, lightly myelinated fibers; transmit at 15 m/s (~30 mph).
  • Group C fibers: Smallest diameter, unmyelinated; transmit at 1 m/s (~2 mph).
  • B and C groups include ANS visceral motor and sensory fibers that serve visceral organs.

Clinical Imbalance: Impaired AP Impulse Propagation

• Impaired AP impulse propagation can be caused by various chemical and physical factors.
• Local anesthetics act by blocking voltage-gated Na^+ channels.
• Cold temperatures or continuous pressure interrupt blood circulation and delivery of oxygen to neurons.
  • Leads to conditions like cold fingers getting numb or a foot "going to sleep."