Molecular Neurophysiology Quiz

Lecture Molecular Neurophysiology "Excitable Membranes"

• The lecture was held at ETH Zurich on the topic of excitable membranes.
• The professor is Dr. Gerhard Schratt.
• The semester is FS 2024.

Molecular Neurophysiology: From Molecules to Systems

• The course covers molecular neurophysiology from molecules to systems.
• The exam is scheduled for January 13, 2024.
• The exam is online, multiple choice.
• Lecture schedule covers topics like introduction, excitable membranes, action potential, neurotransmitter release, postsynaptic responses and trans-synaptic signaling.
• Other topics include: neuronal signaling, synaptic plasticity.

Books

• Neuroscience, 5th edition, edited by Purves, Augustine, Fitzpatrick, et al.
• Cellular and Molecular Neurophysiology, 5th edition, by Constance Hammond.

The Functioning of the Nervous System

• The nervous system relies on electrical processes.
• Luigi Galvani's experiments with frog legs demonstrated "animal electricity."
• The biological basis of "animal electricity" involves charged ions, the membrane, and muscle contraction.

Bioelectrical Processes: Electrophysiology

• Electrophysiology measures electrical activity in cells and organs.
• ECG (electrocardiography) measures heart activity.
• EEG (electroencephalography) measures brain activity.
• Electrical stimulation can be used to induce or modulate cellular processes.
• Examples include pacemakers, defibrillators, and cochlear implants.

Basis of Bioelectrical Processes

• The membrane potential underlies bioelectrical processes.
• The membrane voltage is approximately -70mV.
• Inside the cell is negative relative to the outside.
• Nomenclature: membrane voltage is the difference in potential.
• Symbol: Vm = Um = Em.
• Unit is mV.
• Inside vs. outside convention uses the outside as the reference potential (mass = 0 mV).

Functions of the Membrane Potential

• The membrane potential drives transport across membranes (like in the small intestine and kidneys).
• It triggers secretory processes (e.g., insulin secretion).
• It drives ATP synthesis in mitochondrial membranes.
• It is involved in electrical signaling.
• It is a direct trigger for muscle activity

Requirements for Generating a Membrane Potential

• Essential for membrane potential are electrical charges, electrical insulation, and a mechanism to transport charges across the membrane.

Ions: Electrically Charged Molecules

• Salts dissociate into electrically-charged ions in water (cations + and anions -).
• Physiological salt solutions have equal amounts of positive and negative charges.

Intra- and Extracellular Ion Concentrations

• Intracellular and extracellular environments have different ion concentrations.
• Specific concentrations are listed for various ions (Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, A- (e.g., proteins)).

Requirements for Membrane Potential (repeat)

• Electrical charges, electrical insulation, mechanism for moving charges across the membrane.

Intra- and Extracellular Environment

• The plasma membrane separates the intracellular and extracellular environments.
• The membrane is a key component to maintain gradients.
• Hydrophobic nature of the membrane makes it a good insulator for charged ions
• Various principles apply across membranes.

Permeabilities of Physiologically Relevant Solutes

• Cell membranes act as barriers for most polar molecules.
• Permeabilities vary significantly for different types of molecules (gases, small uncharged molecules, water, large uncharged molecules, ions, charged polar molecules)
• Specific values (1 cm/s to 10-12cm/s) are examples of permeability.

How is a Membrane Potential Generated?

• Two essential factors are concentration gradients of specific ions and selective permeability of membranes.
• The result leads to an electrical gradient (membrane potential)
• Other relevant factors are: the concentration difference and the permeability of the membrane.

How Are Concentration Gradients Generated?

• Concentration gradients are the result of transport mechanisms across membranes including diffusion, carrier-mediated transport, facilitated diffusion and active transport (like Primary and secondary active transporters).

How is a Membrane Potential Generated (Repeat)

• The key factors that drive formation of a membrane potential are concentration gradient for a given ion and selective permeability of the membrane to the same ion.

Potential Equilibrium

• The equilibrium potential is a specific voltage at which there is no net ion flux.
• The Nernst equation defines this voltage.

Example Calculation of Equilibrium Potentials

• Illustrates the Nernst equation calculation for specific ions (K+, Cl-).

Summary Equilibrium Potential

• The voltage across a membrane is the equilibrium potential if there is a concentration gradient for an ion.
• The membrane is selectively permeable to the ion.
• Magnitude is defined by the Nernst equation.
• Value depends only on concentration gradient.
• Ion fluxes during potential generation don't significantly change intra/extracellular concentrations.

Signal Transmission: The Action Potential

• Neurological signal transmission utilizes action potentials.

When Does a Cell Fire an Action Potential (AP)?

• Action potentials are triggered by depolarization.
• A threshold potential must be reached for an action potential to occur.

The Action Potential

• Action potentials are characterized by amplitude and kinetics.
• Described as all-or-nothing. The action potential and the phases (rising phase, overshoot, falling phase, and after-hyperpolarization).

Basic Properties of Action Potentials

• Cause of rapid depolarization phase (including membrane potential reversal).
• Triggering of action potentials by depolarization.
• Significance of the threshold potential and the "all-or-nothing" principle.

Classical Experiments on Ionic Mechanisms of APs

• Hodgkin and Huxley's experiments using giant squid axons provided insights into the ionic mechanisms behind action potentials
• Awarded a Nobel Prize.

Mechanistic Principles of Depolarisation and Repolarisation

• Changes in membrane potentials involve ion fluxes that reverse the charge across the membrane.
• The inward current during depolarization, and the outward current during repolarization.

Na+ and K+ Currents

• Na+ and K+ currents are characteristic of action potentials.
• These currents are measured using a voltage-clamp technique.
• The currents result from selective channel openings.

Summary: Generation of an AP

• Depolarization is caused by voltage-gated Na+ channel activation.
• Repolarization involves voltage-gated K+ channel activation and inactivation of Na+ channels.
• The crucial factor is the differential timing of Na+ and K+ conductances.

Why Are Aps Following the "All-or-Nothing Principle?"

• Depolarization increases Na+ permeability, leading to more depolarization (positive feedback).
• The delayed increase in K+ permeability causes repolarization (negative feedback).

Why Are Na+ and K+ Currents Voltage-Dependent?

• The question of the mechanism behind the voltage-dependence of currents.

The Architecture of Voltage-Gated Na+ and K+ Channels

• The structure of voltage-gated channels, including the S4 helix and other domains, and their role in conductance.

Voltage-Dependence of Single Ion Channels

• The open probability of ion channels increases with increasing depolarization.

Molecular Basis of Voltage-Dependent Switch Behaviour

• S4-Helices, with their charged amino acids, act as voltage sensors within voltage-gated channels.

Voltage-Dependent Na+ Channels Adopt States

• Na+ channels cycle through three states: closed, open, and inactivated.
• Inactivation is essential for the action potential.
• The recovery from inactivation.

Consequence of Na+ Current Inactivation

• Describes the absolute and relative refractory periods.

Local Anesthetics Block Na+ Channels

• Local anesthetics block voltage-gated Na+ channels.

How is Signal Transmission Within Neurons Achieved?

• Signal transmission in neurons involves action potentials and synapses

The Function of Nerve Cells

• Signal transmission (action potentials) in neurons.
• Signal transfer (synapses) between neurons.

In Electrically Excitable Cells

• Electrical signals are used for information transfer in nerve cells, heart and other excitable structures.

Signal Transmission without Action Potentials

• Passive properties of axons.
• Signal attenuation along the axon.

Signal Transmission with Action Potentials

• Action potentials enable long-distance signal transmission.
• Signal transmission is not attenuated by action potentials.

Continuous, Regenerative Spread of APs along the Axon

• Action potentials propagate along the axon.
• The spread is regenerative at each segment of the axon membrane.

What Determines the Speed of Signal Spread?

• Factors influencing action potential speed: the axon's diameter and myelination.

Axons with Large Diameter Conduct Faster

• Larger diameter axons conduct faster because of reduced internal resistance.

What Determines the Speed of Signal Spread (repeat)

• Factors impacting AP conduction speed: fiber diameter, membrane resistance and myelination.

Myelinated Axons

• Myelinated axons increase the speed of conduction.
• Myelination involves Schwann cells in the peripheral nervous system, and oligodendrocytes in the central nervous system.

Consequence of Myelination: Saltatory Signal Transmission

• Action potential propagation in myelinated axons.
• Saltatory transmission means jumping across the myelin segments.

Summary Conductance Speed

• Factors affecting action potential speed include axon diameter, membrane resistance and myelination.

Fiber Types and Conductance Speeds

• Different types of nerve fibers (A, B, C) have varying myelination and conduction speeds.

Demyelination Diseases

• Demyelination diseases like Multiple Sclerosis and Guillain-Barré Syndrome impair action potential transmission.

Test your knowledge on the essential concepts of membrane potential and its significance in the nervous system. This quiz covers various topics including bioelectrical processes, neuronal signaling, and muscle cell function, specifically designed for students studying Molecular Neurophysiology.