Action potentials

• Galvani and Galvani (1781)


  Found that electricity through the nerves made the frog's leg muscles contract
• Aldini (1802)


  Used criminal corpses and found the same occurred in humans
• Electricity basics


  Current = flow of charged particles. Like charges repel, opposite charges attract. Voltage = measure of how much potential there is for charge to move, how much stored electrical energy (similar to water pressure).
• Ohm's law - conductance


  current = potential * conductance

  Conductance - measure of how well a charge can flow. Amount of current that flows depends on how much potential there is i.e. stored energy? how big is battery?
• Ohm's law - resistance


  current (amps) = potential (volts) / resistance

  Resistance - how much a material resists current flow
• Conduction in nerves different to in wires

  Helmholtz (1849) used frog sciatic nerve to measure the speed of the nerve and time to constrict the muscle. Found it was about 30-40m/s (1mil times slower than in a wire)
• Current flow in nerves

  Charged particles don't travel far in a nerve when stimulated, close enough to activate processes in the next segment of axon that the charge continues to flow. More detailed info on action potential in next set
• How do cells signal electrically?

  Movement of ions (electrically charges particles), i.e. Sodium (Na+) chloride (Cl-), potassium (K+), Calcium (Ca2+). All different sizes. Some ion flow happens at rest (gets neuron ready to send electrical signal), some happens during signalling
• The cell membrane


  Cells have baseline voltage dif due to water being slightly polarised (neg oxygen and pos hydrogen) meaning charged things can bind to it and ions etc are water-soluble. Tails are hydrophobic so water-soluble things can't get through.

  
• Concentration gradients


  Outside: high in Na+, Cl- and some Ca2+ (therefore low in K+) - positively charged

  Inside: high in proteins (neg charged, too big to go through membrane) and K+ (therefore low in Ca+, Cl- and Ca2+) - negatively charged
• Ion channels and concentration gradient (K+)


  'Holes' in the membrane where some ions can 'leak' through - ones for specific ions i.e. K+

  
• Electrical gradient


  Some potassium leaves, so the inside is now more negatively charged and the outside more positive. This makes it harder for more potassium to leave (like charges repel)

  
• Equilibrium potentials


  Potential across membrane where there is no net flow of an ion, equilibrium potential (E) dictated by concentration difference and ion charge.
• Potassium equlibrium potential


  E = -80mV (below the resting membrane potential). Lots of K inside the cell, so tends to leave, membrane potential has to be v negative to stop it leaving (-80mV)

  
• Sodium equilibrium potential


  E = +62mV (much above resting). Lots of sodium outside the cell, so tends to go inside - will do so very readily when inside neg in relation to outside. Stops entering when membrane becomes really positive

  
• Chloride equilibrium potential


  E = -65mV (just under resting) Lots of chloride outside the cell, so the concentration gradient causes chloride to enter the cell, but the negative potential of inside the cell repels the chloride entry.

  
• Nernst equation


  Used to calculate the equilibrium potential for an ion (don't need to know the actual equation). Says that the equilibrium potential for an ion depends on the temperature, the charge on an ion, and the concentration gradient across the membrane of an ion.
• Membrane potential (mp)


  Set by electrochemical gradient and permeability of membrane to different ions. If permeability of certain ion increases, potential moves towards equilibrium potential for that ion. If only K+ channels open, leaves until mp about -80mV. If only Na+ channels open, enters until mp about +60mV. At rest, more K+ open than Na+, so mp is closer to K+ equilibrium potential (-70mV to be exact)
• Maintaining ion gradients - sodium-potassium pump

  Uses ATP energy. Ion fluxes during AP don't use energy as they are just travelling down electrochemical gradient. Putting them back moves against this gradient, which requires energy from ATP. For every 3 Na+ pumped out, 2 K+ are pumped back in.

  
• Neurotransmission


  INTRAcelluar transmission = electrical

  INTERcelluar transmission = chemical.
• Depolarisation VS hyperpolarisation


  Depolarisation = becomes more positive

  Hyperpolarisation = becomes more negative
• Changing membrane permeability - ion channels


  Some open all the time (i.e. K+ channels), some opened by dif stimuli e.g. change in voltage or binding specific molecules.

  Voltage-gated SODIUM (Na+) channels activated at -55mV

  Voltage-gated POTASSIUM (K+) channels activated at +30mV
• Generation of action potential

  Due to wave of transient depolarisation of the cell's membrane. It conveys a fast signal from one place to another in the body and is generated by changes in membrane permeability due to opening and closing of voltage-gated ion channels

  
• The action potential


  It is a self-regenerating electrical wave. It is also a transient change (takes about 1ms) in membrane potential. The action potential only occurs if athresholdmembrane potential is achieved in the axon hillock, which transiently opens voltages-gated sodium channels

  
• Events of action potential (AP)

  1. Threshold potential is reached

  2. Depolarisation due to the opening of sodium channels

  3. Repolarisation due to inactivation of sodium channels and open of voltage-gated potassium channels

  4. Hyperpolarisation as leak channelsandvoltage-gated potassium channels are still open

  5. Sodium channels released from inactivation (can fire AP again). Potassium channel also closed which brings back to RMP

  Very few ions move during an action potential as it barely changes the conc. gradients (as long as keep pumping the ions back)

  
• periods

  
• Absolute


  refractory periodAllsodium channels are inactivated (unable to respond to other stimulus, regardless how strong) which enforces one-way transmission
• Relative


  refractory periodSomesodium channels are inactivated meaning only very strong stimuli could re-open the sodium channels and create an action potential
• Action potentials are


  all or nothingThey either happen or they don't!. For one to be generated, local depolarisation must reach a threshold point, which is the voltage at which sodium channels start to open.

  
• Action potential propagation (transmission)

  Action potentials (APs) transmit along axons at the same size. As it moves, it depolarises the next section of membrane and opens the sodium channels - if enough are open then it reaches the threshold ad continues transmitting along the axon. Area where AP has just been generated cannot fire again due to inactive Na+ channels.
• AP transmission speed


  Ranges from 0.1m/s to 100m/s.
• Why is AP speed so variable - Speed of membrane potential change to reach threshold

  Affected by the resistance of the membrane (will be slower if more charge can leak out) and the capacitance of the cell (will change how easy it is to change membrane voltage e.g. if high capacitance, a lot of charge will be needed to create change)
• Why is AP speed so variable - how far depolarisation spreads along axon

  Affected by membrane resistance (if membrane is more leaky, the depolarisation doesn't spread as far) and diameter (if the diameter is larger, it will conduct faster - more room so less likely to bump into stuff, therefore go faster)
• AP in unmyelinated axon

  Depolarisation dissipates before travelling very far down the axon. Needs lots of sodium channels close to each other so that the next section of membrane can be depolarised

  
• AP in myelinated axon


  Well-insulated by myelin sheath. Very low leakiness of current (except for at Nodes of Ranvier (NoR) with lots of sodium channels). Depolarisation can 'jump' across the myelin sheaths before being regenerated by opening Na+ channels at NoR.

  
• Myelination


  Myelin insulates the membrane so there is less charge loss. It is known assaltatory conductionwhen then AP travels from one NoR to the next. APs with myelinated axons are faster and more efficient, meaning less ions flow and therefore less ATP needed to pump them back.
• Synapse


  The small gap between neurons, including the pre-synaptic membrane, the actual gap (aka synaptic cleft), and the postsynaptic membrane.
• Synaptic transmission; step 1

  Action potential arrives at the end of the axon... the axon terminal
• Synaptic transmission; step 2

  The depolarisation of the axon terminal opens voltage-gated calcium channels. These are activated when the membrane potential reaches -10mV (more depolarisation than sodium channels) - calcium enters the cell

  
• Synaptic transmission; step 3

  Calcium causes the vesicles to fuse with the axon terminal membrane and release neurotransmitters. A neurotransmitter is a molecule that transmits info between neurons