Nervous System Anatomy & Physiology - PHR2001

Nervous System Anatomy and Physiology

• Course: PHR2001
• Date: 27/09/2024
• Time: 10:00 AM – 1:00 PM
• Instructor: Dr. Richard Ngomba
• Course Code: NDH1010 & MB0312
• Location: University of Lincoln, School of Pharmacy

Workshop Material (Week 4 - Neurophysiology)

• The workshop materials cover neurophysiology.

Ohm's Law

• Voltage (V) = Current (I) × Resistance (R)
• Voltage: forces current around the circuit (-70mV)
• Current: flow of ions (K⁺)
• Resistance: governed by the number of ion channels present and how many are open

Capacitance

• The ability of the cell membrane to store charge.

Measuring Membrane Potential

• A microelectrode and a reference electrode are used to measure the resting potential
• The resting potential is -80 mV.

Intracellular Glass Microelectrodes

• Cells are small making it difficult to get access inside
• The first glass microelectrodes were developed by Ling and Gerard in 1949.

The Resting Membrane Potential

• Requires:
  • Intact cell (semi-permeable) membrane
  • Ionic concentration gradients, particularly K⁺ ions
  • Metabolic processes over the long term
• Julius Bernstein (1880s) described the ionic theory, Nernst equation and semi-permeable membrane

Ionic Concentration Gradients

• Intracellular: 12 mM Na⁺, 125 mM K⁺, 5 mM Cl⁻, 108 mM anions
• Extracellular: 120 mM Na⁺, 5 mM K⁺, 125 mM Cl⁻
• Plasma membrane is impermeable to Na⁺

Equilibrium and Resting Potential

• At equilibrium, there's balance between K⁺ ions moving in and out.
• This happens at the resting potential, -80mV.
• The concentration gradient opposes the electrical gradient for K⁺.

Simple Models of Ion Flow

• Equal concentrations: No voltage difference, no net movement
• Unequal concentrations: Voltage difference (positive/negative) between compartments, net ion movement
• Selective membrane (e.g., permeable to K+ but not Cl-) establishes a voltage difference.

Nernst Equation

• Used to calculate the equilibrium potential (E_k) for an ion.
• 𝔼_k = RT/ZF log10 ([K⁺]_out / [K⁺]_in)
• RT/ZF ≈ 58mV at room temperature for monovalent ions
• A 10-fold difference in K+ concentration inside versus outside corresponds to a -58mV membrane potential

How Membrane Potential Changes with K⁺

• Reducing the K⁺ concentration gradient leads to a decrease in the membrane potential towards resting potential.

Other Ion Contributions to E_m

• The membrane is ideally impermeable to Na⁺ ions. Changes in Na⁺ concentration do not affect resting potential.

ATP-Dependent Ion Pumps

• Maintain ionic gradients (e.g., Na⁺/K⁺ pump)
• The Na+/K+ pump uses ATP to move 3 Na+ ions out and 2 K+ ions in creating an electrochemical gradient.

Quizzes (Examples)

• Mitochondria: Mitochondria produce ATP for cellular energy, not cytoplasm or glucose
• Action Potential Location: Voltage-gated Na⁺ channels are primarily located at the axon hillock.

Transport Across Cell Membranes

• Diffusion (passive)
• Facilitated diffusion (passive, uses carrier proteins)
• Active transport (requires ATP)

Types of Channels

• Voltage-gated: Activated by changes in membrane potential
• Mechanically-gated: Activated by mechanical forces
• Ligand-gated: Activated by binding of a specific molecule (ligand)
• Leak channels: Always open allowing ions to flow passively.

Membrane Bound Proteins & Location of Channels

• Na⁺/K⁺ ATPase (membrane bound protein)
• Voltage-gated Na⁺ channels: axon hillock & unmyelinated axons
• Mechanically/stretch-gated Ca²⁺, Na⁺ channels: Cell body and dendrites
• Ligand-gated channels (e.g., ACh, GABA etc.): dendrites & cell body
• Leaky channels: in most cell membranes

Action Potential Changes

• Action potential includes depolarization, repolarization, and afterpotential phases.

Sodium Influx during Action Potential

• The rapid influx of Na⁺ ions initiates and maintains depolarisation during the action potential
• The membrane is permeable to Na⁺ ions for a brief moment
• Na+ concentration gradient is the main driving force, also the electrical gradient

What Initially Depolarizes Neurons to Open Voltage-Gated Na⁺ Channels

• Synaptic transmission (EPSPs)
• Generator (receptor) potentials (sensory neurons)

Na⁺ Channel Opening: Regenerative

• Depolarization opens Na⁺ channels allowing Na⁺ influx
• This positive feedback loop makes the action potential self-regenerating

Action Potentials and Thresholds

• Action potentials need to reach a threshold voltage before they can begin

Repolarization

• The returning phases of the action potential (from the peak to its resting state)
• Repolarisation is due to voltage-gated K+ channels opening slowly after Na+ channels open and inactivate. Then the K+ ions flow out

Ion Flow During Action Potential

• Shows how Na+ and K+ conductances change over time, causing the membrane potential to fluctuate.

Signal Transmission (along axon)

• Neuron depolarizes at stimulus site
• Depolarization moves signal down the axon.

Refractory Period

• Absolute refractory period: Neuron cannot be re-stimulated; Na+ channels are inactivated.
• Relative refractory period: Needs greater stimulation to initiate an action potential, K⁺ channels are still active.

Saltatory Conduction and Myelin Sheath

• Saltatory conduction involves action potentials jumping between nodes of Ranvier in myelinated neurons.
• Myelin sheath speeds up action potential propagation

Synapse

• Junction between nerve cells.
• First (presynaptic) cell release chemical neurotransmitter to trigger second (postsynaptic) cell.
• Drugs often affect nerve cell communication at the synapse

Reflex Arc

• Simplest nerve circuit, doesn't require higher-level processing
• Five parts: receptor, sensory neuron, integration center (spinal cord), motor neuron, effector.

This quiz focuses on the anatomy and physiology of the nervous system, particularly covering neurophysiology topics outlined in the PHR2001 course. Key concepts such as Ohm's Law, capacitance, measuring membrane potential, and the use of intracellular glass microelectrodes will be explored. Prepare to test your understanding of these critical topics!