Quiz 2 BNA

• Resting membrane potential


  Electrical charge in the cytosol of the axon is carried by electrically charged atoms - ions
• Components of the neural membrane

  • Neural membrane
  • Ion channels
  • Action potential
  • Role of ion channels in generating the action potential
  • Action potential conduction and neural integration
  • Neurotransmitter synthesis
  • Synaptic transmission
• Neurons


  • Solve the problem of conducting information over a distance by using electrical signals that sweep along the axon
• Action potential


  A special type of signal that does not diminish over distance, has a fixed size and duration, and information is encoded by the frequency of action potentials of individual neurons
• Excitable membrane


  When a cell with an excitable membrane is not generating impulses it is said to be at rest, and the cytosol along the inside of the surface of the membrane has a negative electrical charge compared with that of the outside
• Cytosol and extracellular fluid


  Water is the main ingredient, and water is a polar molecule making it an effective solvent of other charged or polar molecules
• Ions


  Atoms or molecules that have a net electrical charge, including Na+, K+, Ca2+, and Cl-
• Neural membrane


  • Phospholipid bilayer acts as a relatively impermeable barrier between the inside and outside of the cell, and membrane proteins can assemble to form pores (ion channels) or ion pumps
• Hydrophilic


  Ions and polar molecules that are "water loving"
• Hydrophobic


  Compounds whose atoms are bounded by nonpolar covalent bonds (shared electrons are shared evenly) and have no basis for chemical interaction with water, or "water fearing"
• Phospholipid bilayer


  Contains long non-polar carbon chains bounded to hydrogen atoms, and a polar phosphate group attached to one end of the molecule, forming a sheet of phospholipids two molecules thick that isolates the cytosol of the neuron from the extracellular fluid
• Protein structure


  • The sequence in which the amino acids are linked together determines the primary structure, the way the chain bends or folds is the secondary structure, further bending and folding creates the tertiary structure, and different polypeptide chains can bond together to form a large molecule with a quaternary structure
• Channel proteins


  Membrane-spanning protein molecules that can assemble to form pores (ion channels) in the phospholipid bilayer
• Ion channels


  • Are made from membrane-spanning protein molecules, a functional channel requires 4-6 similar protein molecules to assemble and form a pore, and they have the important property of ion selectivity specified by the diameter of the pore and the nature of the R groups
• Gating


  Ion channels that can be opened and closed by changes in the local microenvironment of the membrane
• Diffusion


  The net movement of ions from regions of high concentration to low concentrations, driven by the random motion of ions and molecules dissolved in water
• Electricity


  An electric field can induce a net flow of ions in a solution, and the amount of current (I) that flows depends on the electrical potential (V) and the electrical conductance (g)
• Resting membrane potential


  The voltage across the neural membrane at any moment, typically around -65mV, with the inside of the membrane being negatively charged relative to the outside
• Equilibrium potential


  The electrical potential that exactly balances an ionic concentration gradient, where the diffusional and electrical forces are equal and opposite
• Nernst equation


  Calculates the equilibrium potential (EP) for an ion based on the charge of the ion, temperature, and the ratio of the external and internal ion concentration
• Ion pumps


  Membrane-spanning proteins that use energy from ATP breakdown to transport certain ions across the membrane against their concentration gradient, such as the sodium-potassium pump
• Resting potential


  The membrane potential is close to the equilibrium potential for potassium (Ek) because the membrane is mostly permeable to K+ at rest
• Action potential


  Brief but large changes in membrane potential that originate in the axon hillock and are propagated along the axon, carrying information to postsynaptic targets
• Properties of the action potential

  • Resting, rising (rapid depolarisation), overshoot (inside of membrane becomes positively charged), falling (rapid repolarisation), and undershoot/hyperpolarisation (more negative than resting potential)
• Extracellular recording


  Recording electrode is placed near the membrane, not inside the neuron, and measures the sharp drop in potential as positive charge moves away from the electrode into the cell
• Intracellular recording


  Measures the potential difference between an electrode inside the neuron and another electrode outside the neuron in a bathing solution
• Hyperpolarisation


  The interior of the membrane becomes even more negative relative to the outside
• Depolarisation


  The interior of the cell becomes less negative
• Local potential


  An electrical potential that spreads passively across the membrane, diminishing as it moves away from the point of stimulation
• Placement of a microelectrode into the cell

  1. Studies using squid; large neurons

  2. Microelectrode is often a micropipette filled with a highly conductive salt solution (AgCl, NaCl, KCl)

  3. The electrodes are connected to an amplifier and readings are recorded with an oscilloscope
• Hyperpolarisation


  The interior of the membrane becomes even more negative, relative to the outside
• Membrane potential changes


  • More slowly than current injection because of passive electrical properties of the neuron
  • Local potential: an electrical potential that spreads passively across the membrane, diminishing as it moves away from the point of stimulation
  • Small hyperpolarising and depolarising current injections elicit "passive" membrane potential changes
  • Large depolarising current injection pushes membrane potential over "threshold" and an "active" constant size action potential is generated
• Threshold


  If the membrane potential reaches about -40mV, an action potential is triggered
• Action potential


  • All or none property - neuron fires at full amplitude or not at all, does not reflect increased stimulus strength
  • Information is coded in the frequency of action potentials - increased frequency = increased stimulus strength
  • Afterpotentials are changes in membrane potential after action potentials
• Ionic driving force (DFion)

  Difference between overall membrane potential Vm and the equilibrium potential (Eion) of a particular ion

  DFion = (Vm - Eion)

  Sodium: DFna = (-65-62) = -127mV (large driving force into the cell)

  Potassium: DFk = (-65- -80) = +15mV (moderate force out of the cell)
• Membrane currents and conductances

  Net movement of K+ ions across the membrane is an electrical current Ik

  Number of open potassium channels is proportional to an electrical conductance gK

  Iion = gion (Vm - Eion)
• Movement of ions during an action potential

  1. Voltage gated Na+ channels open - Na+ rushes into the cell (depolarisation)

  2. K+ channels very slowly begin to open

  3. Na+ channels inactive - no more Na+ enters the cell (peak of the AP)

  4. K+ channels are fully open - K+ ions are leaving (repolarisation)

  5. K+ channels begin to close - K+ is still slowly leaving the cell (hyperpolarisation)

  6. K+ channels close - excess ions diffuse away - membrane recovers to resting Vm (recovery)
• Sodium gates


  • Activated (opened) by depolarisation above threshold and inactivated (closed and locked) when the membrane potential acquires a positive potential

  De-inactivated (unlocked) when the membrane potential returns to a negative value
• Voltage gated sodium channel

  Protein making up the sodium channel forms a pore in the membrane that is highly selective to Na+ ions and the pore is opened and closed by changes in the electrical potential of the membrane

  The molecule has four distinct domains (I-IV) with each domain consisting of six transmembrane alpha helices (S1-S6)

  At S4 there is a voltage sensor

  Pore loop also contributes to the selectivity filter

  The 4 domains are believed to clump together to form a pore between them

  Pore is closed at the negative resting potential

  When the membrane is depolarised to threshold the molecule twists into a new configuration allowing Na+ through the pore
• Selective filter of sodium channel

  • Like K+ channel, sodium channel has pore loops that are assembled into a selective filter - makes Na+ channel 12x more permeable to Na+ than K+

  Na+ ions are stripped of their associated water molecules as they pass the channel

  The retained water serves as a molecular chaperone for the ion - necessary for the ion to pass the selective filter

  The ion-water complex can then be used to select Na+ and exclude K+