Neural Transmission
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Neural Transmission Presentation Transcript

  • 1. Neural Transmission Part I – The Neuron at Rest
  • 2. How a Nerve Impulse is Transmitted
    • Impulses travel along nerve cells and from cell to cell.
    • These impulses are transmitted electrically within a neuron and chemically from cell to cell.
  • 3. Electrical Signals ~ Key Ideas
    • Information is carried by waves of impulses or spikes called action potentials
      • The information is coded by the time and location of the action potential, not its size.
    • When no signaling is going on, energy must still be expended to maintain the system
      • about 70% of energy used by the brain is for this maintenance
  • 4. Why Electrical Transmission?
    • The long distances and short times required for effective functioning of the nervous system requires electrical signaling.
    • Neurons are poorly insulated, badly conducting wires that are "shorted out" by sitting in conductive fluid.
    • The outside of neurons is more conductive than the inside.
    • Thus the mechanism for electrical signaling must be different from that used by a copper wire.
  • 5. Background Information
    • The electrical operation of neurons occurs in an aqueous medium
    • Water is a polar solvent
      • Dissolves polar solids like salt (NaCl)
      • Polar molecules have charge separation on the molecule, i.e. they have electrical polarity
      • Non-polar molecules have no charge separation
  • 6. The Importance of Ions
    • The dissolved substances of interest are sodium, potassium, calcium, and chloride (also dissolved proteins)
      • Exist as ions
      • Cations - positively charged : Na + , K +, Ca ++
      • Anions - negatively charged : Cl -
    • Ions in water are surrounded by a sphere of water molecules so they aren't as small as one might think
  • 7. Properties of the Cell Membrane
    • The cell membrane is a phospholipid bilayer
    • Phospholipid bilayer is amphipathic
      • Has both polar hydrophilic zones and non-polar hydrophobic zones
    • The hydrophobic lipid tails are on the inside
    • The hydrophilic phosphate heads stick out into the aqueous environment
    • Proteins are embedded in the bilayer
      • Embedded proteins can form ion channels or receptors
  • 8. Electrical Properties of the Membrane
    • There is an unequal distribution of Na + , K + , Cl - and organic anions across the membrane
    • At rest, there are 10x as many Na + ions outside the axon as inside.
    • Inside the axon are negatively charged ions
    • The membrane keeps Na+ ions outside, negative ions inside.
    • K+ passes freely over the membrane, so there are 20x as many K + ions inside the membrane as outside.
  • 9. Electrical Properties of the Membrane
    • Thus the inside of the cell membrane is negatively charged relative to the outside
    • Therefore the axon is polarized
    • This produces voltage
  • 10. The Resting Potential
    • Neurons have charge difference of about -65 mV across the plasma membrane
      • Outside charge is defined as 0
    • This comes from the concentration gradient and the high permeability of K + , low permeability of Na +
      • K + tends to move out of the cell because of the concentration gradient, leaving the inside negative
    • Changes in resting membrane potential can serve as a signaling mechanism
      • Serves as a baseline from which change is sensed
    • Differs in different cells; range of -40 to 80 mV
    • Neural signals are changes in this resting potential.
  • 11. Maintaining Membrane Potential: Ion Channels and Ion Pumps
    • To maintain the membrane potential ions must move into or out of the cell
    • Ion channels - pores in cell membrane specific for a given ion: Na + channels, K + channels, Cl - channels, etc.
    • Ion pumps - enzymes embedded in membrane that use energy from ATP to pump Na + out and K + in, or to pump Ca ++ out or cell. 
  • 12. The Sodium Potassium Pump
    • The unequal distribution of ions is maintained by membrane proteins that serve as a pump
    • Transport Na + in, K + out
    • Pump keeps Na + concentration low inside the cell; 10x higher outside than inside
    • K + concentration kept low; 20x higher inside than out
  • 13. Movement of Ions
    • Diffusion - movement down a concentration gradient from an area of higher concentration to an area of lower concentration
    • The diffusion pressure for each type of ion is balanced by an electrical force from the voltage that develops across the membrane.
    • Electric fields - movement of ions, as charged particles, in response to an applied voltage
  • 14. Defining Electrical Terms
    • Voltage (V) - electrical potential between an anode and cathode (volts or millivolts)
    • Current (I) - flow of charged particles, including ions (amperes)
    • Conductance (g) - measure of the ease of movement of charged particles (siemens)
    • Resistance (R) - 1/conductance, measure of resistance to movement of charged particles (ohms)
    • Ohm's Law - V = IR or I = gV
  • 15. Equilibrium Potentials
    • If a gradient exists across a membrane which is permeable to an ion:
      • Ions will move across the membrane through ion channels from high concentration to low concentration
      • A voltage will develop at the membrane which opposes the movement of that ion
    • At equilibrium the force of diffusion is balanced by the electrical force from the voltage that develops across the membrane.
    • The voltage that exactly balances each ion is the equilibrium potential for that ion.
  • 16. Notes on the Equilibrium Potential
    • If a cation is causing the potential, there must also be an anion in solution.
      • A potential will only develop if the membrane is impermeable to the anion.
    • In neurons, it is the existence of the A - proteins, which cannot cross the membrane, that indirectly causes the resting potential!
    • Membrane potential is a weighted average of equilibrium potentials
    • The more permeable the membrane is to a given ion, the closer the membrane potential will be to the equilibrium potential for that ion
  • 17. The Nernst Equation
    • Gives a numerical value of the equilibrium potential
    • E ion = 2.303 (RT/zF) log([ion] o /[ion] i ) 
    • Where:
      • E ion = equilibrium potential for a given ion
      • R = gas constant
      • T = temperature in degrees Kelvin
      • z = charge of the ion
      • F = Faraday's constant
      • [ion] o = ionic concentration outside neuron
      • [ion] i = ionic concentration inside neuron 
  • 18. Solving the Nernst Equation
    • At body temp. (37 o C) the Nernst equation gives:
    • E K+ = 61.54 log([K + ] o /[K + ] i )
        • = 61.54 log(5/100)
        • = -80 mV
    • E na+ = 61.54 log([Na + ] o /[Na + ] i )
        • = 61.54 log(150/15)
        • = +62 mV
  • 19. Solving the Nernst Equation (Continued)
    • E cl- = 61.54 log([Cl - ] i /[Cl - ] o )
        • = 61.54 log (13/150)
        • = -65 mV
    • E ca++ = 30.77 log([Ca ++ ] o /[Ca ++ ] i )
        • = 30.77 log(2/.0002)
        • = +246 mV
  • 20. The Goldman Equation
    • The membrane potential is a weighted average of the equilibrium potentials
    • Calculated from the Goldman Equation
    • V m =
      • 61.54 log{(P K [K + ] o +P Na [Na+] o )/(P K [K + ] i + P Na [Na + ] i )}V m
      • = 61.54 log{(40[5]+ 1[150])/(40[100] + 1[15])}
      • = -65 mV 
    • The Goldman equation means that the more permeable the membrane is to a given ion, the more that ion's equilibrium potential will dominate the membrane potential.
  • 21. The Computational Goldman Equation
    • Neurophysiologists generally use another equation based on a circuit model of the cell membrane
    • This uses conductance and equilibrium potential directly.
    • The “computational” form of the Goldman Equation: 
      • V m = (g K E K + g Na E Na )/(g K + g Na )
    • This equation shows that as the conductance to either potassium or sodium increases, the membrane potential approaches the equilibrium potential for potassium or sodium.
  • 22. Neural Transmission Part II – The Action Potential
  • 23. The Action Potential
    • A change in membrane potential causes an action potential
      • increase in membrane potential = hyperpolarization (inhibitory; less likely to send signal)
      • decrease in membrane potential = depolarization (excitatory)
    • Action potential = small electrical change that propagates along the axon
      • The conducting signal of the neuron
  • 24. Transmission of a Nerve Impulse
    • When the nerve fiber is stimulated, membrane becomes permeable to Na + ions
    • Na + rushes inside changing the electrical charge.
    • Neuron is depolarized
    • This creates an action potential .
      • Only lasts .5 millisecond.
    • Action potential moves down the nerve fiber.
      • This electrical wave = nerve impulse (the movement of the action potential along a neuron)
  • 25. Stages of Neural Transmission
    • Input Signal & Initiation
    • The Trigger
    • Conduction Component
    • Output
  • 26. The Input Signal
    • Threshold - to fire a neuron, the impulse must have certain level of strength. This is yes or no; not a continuum.
    • Begins when membrane potential in the postsynaptic neuron is turned on by the output of another (presynaptic) neuron
      • Presynaptic neurons release a chemical transmitter at the synapse between 2 cells
      • Transmitters interact with receptor molecules
    • Receptor molecules transduce chemical potential energy into an electrical signal = synaptic potential
  • 27. Initiation
    • When the nerve fiber is stimulated, conformational changes in ion channels cause the membrane to become permeable to Na + ions
    • Ionic current flows thru open channels, producing changes in the resting potential of the cell membrane
    • Change in membrane potential = input signal
      • Can vary in amplitude & duration
    • Receptor potential spreads along the axon
      • Decreases with distance
      • A purely local signal which must be amplified or regenerated to reach rest of nervous system
  • 28. The Trigger
    • When the membrane is depolarized, channels open & sodium rushes in
    • Action potentials are generated by the influx of Na + ions
    •   The input signal is spread passively
    • If the signal exceeds the threshold, it proceeds; signal is all or none:
      • stimulation below threshold  no signal
      • all stimulation above threshold  same signal
  • 29. Ion Channels are Voltage Sensitive
    • Depolarization of one area of the axon results in depolarization of the next area
    • This occurs because ion channels are voltage-gated
    • The ion channels controlling Na + and K + can be in four states
  • 30. Resting State Neither Channel is Open.
  • 31. Threshold Voltage potential to begin opening Na + channels is reached
  • 32. Depolarizing Phase Na + channels open, K + channels closed
  • 33. Repolarizing Phase Na + channels close and K + channels open
  • 34. Undershoot Na + channels closed; K + channels still open – gates haven’t responded to repolarization
  • 35. Action Potential Theory vs. Reality
    • Reviewing the Theory:
      • When the membrane is depolarized to the threshold, there is a transient increase in g Na+
      • This allows entry of Na + ions which depolarize the neuron
      • Subsequent increase in g K+ allows K + ions to leave the depolarized neuron faster
      • This restores the negative membrane potential
  • 36. Testing the Action Potential
    • Measure Na + & K + conductance of the membrane during the action potential
      • Proved difficult
    • Voltage clamp developed by Kenneth Cole made this possible (~1950)
    • Led to the pivotal experiments s of Alan Hodgkin & Andrew Huxley
  • 37. The Hodgkin & Huxley Experiments
    • Clamped membrane potential of axon at a given value
      • Measured currents that flow across membrane
    • Deduced changes in membrane conductance at different membrane potentials
    • Showed that:
      • Rising phase of the action potential was caused by a transient increase in g Na+ & the influx of Na + ions
      • Falling phase of the action potential was associated with an increase in g K+ and an efflux of K+ ions
    • Hypothesized the existence of voltage gated channels more than 20 years before they were actually directly demonstrated
    • Nobel Prize 1963
  • 38. The Patch Clamp
    • Developed in mid 1970's by Bert Sakmann & Erwin Neher The tip of a glass capillary tube (1-5  in diameter) is pressed on the membrane of a neuron
    • Apply suction so a tight seal forms.
    • This leaves ions only one path, thru channels in the underlying membrane patch
    • Measures currents flowing through ion channels in the patch at different imposed voltages
    • Reveals inward or outward currents from membrane channels
  • 39. Significance of Patch Clamp Experiments
    • If the patch contains a single channel. it allows specific measurements
    • Example: lowering membrane potential from – 65 mv to –40 mv would cause Na + channels to open
    • At constant voltage, amplitude of current reflects membrane conductance
    • Duration reflects time the channel is open
    • Showed that most channels flip between 2 conductance states: open & closed
    • Proved the existence of voltage gated channels
    • Nobel Prize in 1991
  • 40. Recording Electrical Events in Neurons: Extracellular Recording
    • A glass capillary tube, tapered to a small tip and filled with NaCl or a fine metal wire or a wet cotton wick - outside axon
    • Measures quick changes in voltage due to extracellular currents as the action potential passes
    • The recorded action potential is biphasic, going one way as the action potential approaches the electrode and going the other way as the action potential passes the electrode and recedes
    • The easiest recording technique
  • 41. Recording Electrical Events in Neurons: Intracellular Recording
    • A glass capillary tube, tapered to a small tip and beveled like a hypodermic needle, filled with KCl penetrates cell membrane
    • Measures quick changes in the membrane potential that constitute the action potential
    • The recorded action potential is monophasic, going from resting potential (-65 mV) toward E Na+ (+62 mV) and then toward E K+ (-80 mV) before returning to the resting potential
    • The smaller the neuron, the harder this is to do
  • 42. Graded Electrical Potentials
  • 43. Conduction
    • Action potential moves down the nerve fiber.
      • Wave of depolarization
    • The signal does not decay fast  100 m/sec.
    • In myelinated neurons ions can only permeate and the impulse can only be passed, at the nodes of Ranvier.
  • 44. Direction of the Action Potential
    • Axon hillock - spike initiation zone
    • Generator potential - spike initiation; analog to digital conversion
    • Typically there are voltage-sensitive ion channels on one side of the axon hillock (the axon side) and no voltage-sensitive ion channels on the other side (the soma or dendrite side)
    • Once an action potential starts moving, the absolute refractory period keeps it going in only one direction
  • 45. Conduction Velocity
    • How far down the axoplasm the current goes before it passes through the membrane and triggers new Na + channels depends on the diameter of the axon
    • the larger the axon, the further the current will go.
    • The larger the axon, the faster conduction velocity
  • 46. Saltatory Conduction
    • In myelinated axons, only the open places at the Nodes of Ranvier allow current to exit.
    • Depolarization "jumps" from node to node = saltatory conduction
    • This gives faster conduction with smaller axon diameter
      • Vertebrates need this or our nervous systems would be enormous
    • Multiple sclerosis and Guillain-Barre syndrome are both demyelinating diseases
      • Removing the myelin disrupts saltatory conduction, and leads to slowed conduction velocity
  • 47. Picturing Saltatory Conduction
  • 48. How Fast Can a Neuron Fire?
    • Since the sodium channels are deactivated for 1 msec after closing, there is an absolute refractory period of 1 msec
      • the maximum firing rate is 1000 spikes/sec
    • The undershoot caused by the potassium channels being open means that in the interval 1 msec to 2 msec after the initiation of an action potential, the amount of depolarization needed to reach threshold is increased
      • relative refractory period  
  • 49. Interpreting Nerve Impulses
    • Amplitude and duration are always the same, regardless of input
      • What determines intensity of sensation is not magnitude or duration of action potentials, but their frequency (how many in an area)
    • If signals all alike, how do neural messages translate to behavior?
      • Message determined entirely by neural pathway in which it is carried
  • 50. Communication Between Neurons
    • Impulses must travel not just along the neuron, but also from neuron to neuron.
    • Adjoining neurons don't touch each other.
    • Space between adjacent neurons = synapse
    • The impulse must cross from the axon of one neuron to dendrites on another neuron.
    • Causes the release of special chemicals that can diffuse across the synapse = neurotransmitters
    • Neurotransmitters generate a new impulse in the next neuron or stimulate an effector
  • 51. Output
    • When the action potential reaches the terminal region, it stimulates release of packets of chemical transmitters
    • Transmitters are stored in vesicles
    • Release their contents by fusing with surface membrane = exocytosis
    • Neurotransmitters can be small molecules: L-glutamate, acetylcholine, or peptides like enkephalin
    • Release of transmitters = output
      • amount determined by number & frequency of action potentials
  • 52. Continuing the Process
    • Transmitter diffuses across the synaptic cleft
    • Binds specific receptors on adjacent neuron
    • Neurotransmitters are reabsorbed and recycled by the cell
    • Electrical signal starts over in the next neuron
    • Controlled by negative feedback
      • returns to resting state