AP L-3/4

• Resting membrane potential (RMP)

  Steady difference in electrical charge across the membrane, with the cytosolic side of the plasma membrane having a negative electrical charge compared to the extracellular side
• Nernst equation

  Calculates the equilibrium potential for a single ion
• Goldman equation

  Predicts the resting membrane potential by accounting for the membrane permeability of different ions
• Sodium-potassium (Na+/K+)-ATPase pump

  Exchanges internal Na+ for external K+, pumping both against their concentration gradients using the energy from ATP breakdown
• Na+/K+-ATPase pump activity

  Maintains the K+ concentration gradient across the membrane, with K+ concentrated inside the cell
• Neuronal membrane at rest

  • Highly permeable to K+ via leak channels, allowing K+ to move down its concentration gradient out of the cell, leaving the inside negatively charged
  • Limited Na+ influx through leak Na+ channels down the concentration gradient
• The resting membrane potential (around -65mV) is not simply a reflection of the equilibrium potential for K+ (around -94mV)
• The Goldman equation predicts a resting membrane potential of around -65mV
• The Nernst equation is more likely to accurately predict the equilibrium potential for a single ion, while the Goldman equation is more accurate for predicting the overall resting membrane potential
• Neurons can be classified as afferent or efferent
• Neurons

  • Functional unit of the nervous system
  • Communicate/convey information from sensors to CNS; store and integrate information; communicate commands from CNS to muscles and glands
• Neurons have become highly specialised to serve two primary functions: the rapid transmission of information from specific sources to selected targets via action potentials, and the integration (summation) of information/electrical activity from many sources
• The anatomy of neurons is directly related to their functions
• Cells capable of generating and conducting action potentials (e.g. nerve and muscle cells) have an 'excitable membrane'
• In a resting neuron, the cytosolic side of the plasma membrane has a negative electrical charge compared to the extracellular side
• Solutes

  Dissolved materials that can move across cell membranes and epithelia, e.g. electrolytes (charged species like Na+, K+, etc.)
• The intracellular (ICF) and extracellular fluid (ECF) differ in their ionic compositions, with K+ more concentrated inside the cell and Na+ and Cl- more concentrated outside
• Membrane permeability

  • Membranes are selectively permeable: highly hydrophobic and impermeable to water, small molecules and ions, but allow passage through channel proteins and carrier proteins
• Passive transport mechanisms

  Transport down the concentration gradient, e.g. simple (passive) or facilitated diffusion
• Active transport mechanisms

  Transport against the concentration gradient, requiring energy (e.g. primary ATP-driven and secondary active transport)
• Concentration gradient


  The difference in solute concentration with distance (in a given direction)
• Electrical potential (V)


  Reflects the difference in charge between the intracellular and extracellular fluid
• Membrane potential (Vm)

  The voltage across the neuronal membrane, which at rest has the inside surface electrically negative compared to the outside
• Equilibrium potential (Eion)

  The potential at which the tendency of an ion to move down its concentration gradient (diffusional force) is exactly balanced by the membrane potential (electrical force), resulting in no net movement of ions
• Action potential (AP)

  A brief reversal of the resting membrane potential, with the inside of the membrane becoming positively charged compared to the outside
• The learning objectives for this lecture are to understand the electrochemical basis of the neuronal resting membrane potential, the use of the Nernst and Goldman equations, how the Na+/K+-ATPase pump generates the ion concentration gradients, and how the relative permeability of Na+ and K+ ions generates the RMP
• The Nernst equation calculates the equilibrium potential for a single ion, while the Goldman equation predicts the overall resting membrane potential by accounting for the membrane permeability of different ions
• The Na+/K+-ATPase pump is critical for brain function as it maintains the K+ and Na+ gradients across the neuronal membrane
• The resting membrane potential results mainly from K+ movement out of the cell via K+ leak channels, as the membrane is highly permeable to K+ at rest
• The learning objectives for the second lecture are to understand the key ionic events during an action potential, action potential propagation and the role of myelin, and the principles of neuronal synaptic transmission and integration of graded potentials
• K+ ions


  Move down their concentration gradient to the outside of the cell, leaving the inside of the neuron negatively charged
• Limited Na+ influx


  Through leak Na+ channels, down concentration gradient, i.e. K+ efflux
• At rest, negative value of the Vm

  Tends to attract K+ into cell. On one hand, K+ leaks out (via leak channels), on the other, the negative charge attracts K+ from ECF into ICF
• Resting membrane potential (RMP)

  The potential at which these 2 opposing drives are balanced, close to EK (but not quite as negative)
• The Nernst and Goldman equations shown are used to predict membrane potentials
• One of the neurons I recorded from (patch clamp technique)
• Learning objectives (lecture 2)

  • The key (ionic) events that occur during an action potential (AP)
  • Pivotal role of voltage-gated Na+ and K+ ion channels
  • Action potential propagation and the role of myelin
  • Principles of neuronal synaptic transmission: How the arrival of an AP at an axon terminal (synapse) results in the release of neurotransmitter(s)
  • Graded potentials and how they are integrated (i.e. summated): Excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs)
• Resting neuron

  The cytosolic side of the plasma membrane has a negative electrical charge, compared to extracellular side. Steady difference in (this) electrical charge across the membrane is called the resting membrane potential (RMP). AP is a brief (quick!) reversal of this condition; i.e. inside of membrane becomes positively charged vs. outside.
• Hodgkin and Huxley (1949) experiments on squid axons revealed the existence of voltage-gated ion channels and their critical role(s) in the generation of APs
• During AP, membrane is more permeable to Na+, than K+ (peak)