Neuroscience: Structure and Function of Neurons

Nervous System - Resting Membrane Potential and Neuron

• Objectives:
  • Understand the basic principles of resting membrane potential generation.
  • Describe the anatomy of a typical neuron and its functions.

Membrane Permeability

• Phospholipid bilayer of cell membranes are impermeable to charged molecules (e.g., Na+, K+, Cl-, Ca++).
• These molecules are also insoluble in the hydrophobic membrane core.
• Large, water-soluble molecules (e.g., proteins, nucleic acids, sugars) also require channels for transport across the membrane.
• Small uncharged polar molecules (e.g., CO2, O2, NH3, and water—mostly via aquaporins) can cross freely.

Electrolytes Distribution

• Interstitial Fluid: Major electrolytes include Na+, Cl-, and HCO3-.
• Intracellular Fluid: Major electrolytes include K+, HPO42- (phosphate ion), and negatively charged proteins.

Dominant Ions and Distribution

• Extracellular fluid: Cations: Na+ Anions: Cl-
• Intracellular fluid: Cations: K+ Anions: Phosphate ions & negatively charged proteins
• Selective permeability of the plasma membrane creates unequal electrolyte distribution, resulting in electrochemical disequilibrium across the membrane.

Electrical Properties of the Cell Membrane

• Plasma membranes act as ionic conductance, allowing ionic currents.
• Concentration gradients dictate ion flow direction across the membrane.
• Membranes act as capacitors, holding charges.
• Electrical gradients generate the transmembrane potential (voltage difference between intra and extracellular spaces).

Generation of Membrane Potential

• At equilibrium, cell and solution are electrically and chemically balanced.
• The cell membrane acts as an insulator, preventing free ion movement between compartments.
• Loss of positive ions (K+) intracellularly, due to Na+-K+ ATPase and K+ leak channels, creates an electrical gradient (more negative ions intracellularly).
• Negative ions and molecules pull K+ back inside the cell.
• Opposing forces (concentration and electrical gradients) balance, resulting in membrane potential measured as equilibrium potential (Eion).

K+ Leak Channels

• Plasma membranes have more K+ leak channels than Na+ leak channels.
• K+ leaks out to the extracellular space due to concentration gradients.
• Negative ions inside the cell follow K+ efflux, due to attraction.
• The membrane's impermeability to negative ions traps negative charges inside the cell.
• K+ leakage through channels contributes to resting membrane potential.

Equilibrium Potential

• Loss of positive ions (K+) intracellularly results in an electrical gradient.
• Negative ions and molecules pull K+ back inside the cell.
• When concentration and electrical gradients balance, net movement is zero.
• The resulting membrane potential is the equilibrium potential.

Resting Membrane Potential

• All living cells have a membrane potential.
• Chemical and electrical disequilibrium exists between intracellular/interstitial fluid at rest.
• Electrical disequilibrium generates an electrical gradient between intracellular and interstitial fluid.
• Transmembrane potential (resting membrane potential) measures electric charges inside relative to outside the cell.
• Resting membrane potential is typically negative in value (due to more negative than positive charges inside).

Stimulation of Plasma Membrane

• A stimulus leads to Na+ influx.
• This depolarization causes the intracellular environment to become more positive.
• Repolarization follows depolarization, returning charges to the baseline.
• Na+-K+ ATPase restores electrolyte distribution to resting conditions.

Resting State of Plasma Membrane

• Some K+ and Na+ leak channels exist in the plasma membrane, especially K+.
• Na+-K+ ATPase is required to maintain ionic concentration gradients.

At Resting State

• Extracellular and intracellular compartments are in a dynamic steady state, not equilibrium.
• They are in osmotic equilibrium but with chemical and electrical disequilibrium; intracellular space has more negative ions.

Equilibrium Potential of a Living Cell

• The Nernst equation can calculate equilibrium potential for a single ion type.
• Variables include: equilibrium potential (Eion), valence (charge, Z), ion concentration outside (extra) and inside (intra) the cell, and constant(2.303 RT/F @ 37°C).

Ion Distribution for K+

• Higher intracellular K+ concentration produces a net efflux of K+ into the extracellular space.
• The tendency of K+ efflux is balanced by negative equilibrium potential (-85.6 mV).

Additional concepts

• Resting state, although a dynamic steady state, is not equilibrium, as it requires energy to maintain ion gradients.
• Depolarization, repolarization, and hyperpolarization are events in which membrane potential changes either more or less negative than the resting membrane potential.

Neuron Anatomy and Function

• Neurons are the functional units of the nervous system, responsible for transmitting and processing information.
• Signals are both electrical (graded, action potentials) and chemical (neurotransmitters) enabling communication between nervous system and body systems.
• Neurons receive information (sensory input), process it (integration), and respond (motor output).

Neuron Types

• Sensory neurons: Typically unipolar or bipolar, carrying information from sensory receptors to the central nervous system (CNS).
• Interneurons Found in CNS, can be anaxonic or multipolar, they integrate sensory information and communicate with other neurons.
• Motor neurons: Multipolar, carrying signals from the CNS to effector organs (e.g., muscles, glands); conveying information, in the form of action potentials toward the effector.

Neuron Structure: Cell body

• Contains nucleus and organelles.
• Occupies a proportionally small volume compared to the whole neuron.
• Proteins produced in the nucleus are transferred outward along the cytoskeleton (microtubules).

Neuron Structure: Dendrites

• Highly branched extensions receiving signals from other neurons.
• Can contain dendritic spines, increasing contact surface area and enabling protein production.
• Signals are propagated from dendrites to the cell body then the axon.

Neuron Structure: Axon

• A single, long projection originating from the axon hillock (trigger zone).
• The axon hillock determines whether electrical signal generated by dendrites travels down the axon.
• Axons branch into axon terminals with synaptic end bulbs.
• These contain neurocrine molecules and mitochondria used to communicate with other cells.

Axonal Transport

• Movement of materials along the axon, essential for transporting neurotransmitters, vesicles, and organelles.
• This transport can be anterograde (away from soma—towards terminal) or retrograde (towards soma).
• The molecular mechanism is associated with motor molecules using ATP.

Neuron Information Transmission

• Information flows from the receiving site (dendrites/cell body) to the axon hillock as graded potentials.
• Electrical signals (action potentials) arise in the axon hillock and are propagated unidirectionally to the presynaptic terminal.
• Axons carry electrical signals unidirectionally, while chemical signals can be bi-directional.