Action Potentials and Synapses

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Action Potentials and Synapses
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Action Potentials

• Most nerves exhibit Action Potentials (APs)
• Spikes of electrical activity
• Almost always less than 1000 per second
• Almost all neurons create APs (some retinal cells
  only have graded potentials)

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Potential

• A potential is the potential to do work.
• Work requires energy.
• The Second Law of Thermodynamics says that all
  matter spontaneously moves towards lower energy
  states. That is, from regions of higher potential
  to regions of lower potential.

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Potential

• There are two major types of energy
• Potential Energy which derives from the four
  basic forces
• Gravity
• Weak force
• Strong force
• Electromagnetic force
• Kinetic energy from moving matter
• The energy that made it move can be extracted.

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Potential

• The two main potential energies of interest to
  neurologists are
• Electromagnetic potential
• Opposite charges attract, like charges repel.
• Concentration potential
• Flow is in direction of higher concentration
  towards lower concentrations until equalization.

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Potential

• Electromotive potential
• Proportional to amount of separated charges

1.5 V Test Ref (0)
-1.5 V Ref (0) Test
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-
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Potential

• Potential difference is the difference in the
  total potentials between the two measured points.
• Potential is measure in volts (V)
• Think of a battery, typically 1.5 or 9 V.
• A 9 V battery has a higher potential than a 1.5 V
  battery.
• Potential is additive
• 3 V
  0 V

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Potential

• Concentration gradient
• Any time there is a concentration gradient, there
  is force trying to move ions to area of lesser
  concentration.

Fresh water (low NaCl) Seawater
(high NaCl)
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Potential

• If you get nothing else out of this lecture
• Opposites attract
• Concentrations equalize

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Cellular Potential

• Because neural cell walls are porous and there
  are differences in ion concentrations inside and
  out, the inside of a neuron has a potential with
  respect to the extracellular fluid.
• Cellular potentials are always given with respect
  to the extracellular space.

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Cellular Potential

• Potential can be calculated by the Goldman
  equation, which takes into account the
  concentrations of the ions Na, K and Cl- and
  their membrane permeabilities.

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Cellular Potential

• Normal nerve potential is about 70 mV with
  respect to the extracellular space.1/20 of a
  battery

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Nerve Cell Environment
A whole lots of Na (sodium) 0 mV
A little Cl-(chlorine)
Cell Lots of K (potassium)
-70 mV
Na ?? K
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Nerve Cell Environment
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Nerve Cell Membrane

• Populated with ion channels
• 4-7 transmembrane domain proteins
• Typically only pass one type of ion
• Activated by ligands, voltage, or time
• Types
• Passive, ionic movement by gradient
• Facilitated transport
• Active transport, energy powered pump

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Transmembrane Transport

• Simple diffusion (spontaneous)
• Ions follow gradients without help
• Facilitated diffusion (spontaneous)
• Helper proteins assist the move
• Active transport (energy required)
• Normally symport 2 ions transported at once
• http//pb010.anes.ucla.edu/membrane.htm

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Transmembrane Transport

• Simple diffusion
• Ions follow gradients without help (Na, K)

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Transmembrane Transport

• Facilitated diffusion
• Larger molecules follow gradients, but have to be
  passively assisted to pass thru membrane. Ex
  glucose transporter

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Transmembrane Transport

• Active transport
• Molecules move against a gradient, so an
  energy-consuming pump is required.
• Symport 2 ions are moved at once. (Na-K pump)

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Action Potential

• There are many types of holes or channels in
  the neural membrane, but the most important are
• Key-activated sodium (Na) channels
• Voltage-activated sodium (Na) channels
• Voltage-activated potassium (K) channels
• Key-activated chlorine (Cl-) channels
• An ATP-powered sodium-potassium pump (symport)

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Action Potential
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Action Potential

• Cell at 70 mV. Normally all channels are closed.
• Something opens keyed Na channels.
• Na enters the cell, depolarizing it.
• When potential reaches threshold (about -40 mV)
  at the axon hillock, many more voltage-controlled
  Na channels open causing a flood of Na
  depolarizing the cell to about 30 mV.
• Na channels close and voltage-controlled K
  channels open, K flows out repolarizing the
  cell.
• Na/K pump restores equilibrium.

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Action Potential

• AP propagation
• The local depolarization triggers the voltage
  controlled pores in the adjacent region, causing
  another depolarization.
• The depolarization progresses along the length of
  the axon.

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Action Potential
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Action Potential

• At the terminals, the depolarization allows Ca
  to enter the terminal and trigger fusion of
  neurotransmitter vesicles to the membrane.
• Neurotransmitter is released via exocytosis.

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Action Potential

• Soluble NSF Attachment protein REceptors (SNAREs)
  keep vesicles in close proximity to membrane.
• Ca causes SNAREs to complete fusion.

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Action Potential

• Amino acid and amine neurotransmitters are
  synthesized in the terminal button.
• All others, including peptides and larger
  proteins, are manufactured in the cell body and
  transported to the terminal button at speeds of
  up to 1 meter per day.
• The latter may suffer periods of insufficient
  neurotransmitter.

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Action Potential

• All or Nothing firing
• Once threshold is reached, the nerve will always
  fire

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Action Potential

• Refractory periods
• Absolute
• About 1 mSec, cannot fire again.
• Due to time-activated gate in Na channels.
• Relative
• About 5-10 mSec, can fire again with more
  stimulation.
• Due to undershoot.

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Action Potential

• Firing rate limited to about 1000 Hz
• Due to absolute refractory period
• Firing rate varies with stimulation, but almost
  never ceases entirely
• Non-quiet presynaptic neurons
• Random molecular motion
• Mechanical forces
• Ionic leakage through nerve wall

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Synapse

• The space between the terminal button of a
  presynaptic nerve and a dendrite, dendritic
  spine, soma or axon of the postsynaptic cell.

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Synapse
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Synaptic Transmission

• The neurotransmitter diffuses across the synapse
  and binds to receptors on the postsynaptic nerve
  dendrites.
• When enough stimulation has been received, the
  postsynaptic nerve fires an AP.
• Presynaptic autoreceptors limit neurotransmitter
  release.
• Excess neurotransmitter is destroyed or reuptaken
  into the presynaptic nerve.

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Synaptic Transmission

• Something opens receptor Na channels
• Neurotransmitters
• From presynaptic cell
• Very localized action
• Neuromodulators
• From nearby cells
• Local area, longer term action
• Hormones
• Transported via blood, not neurons
• Systemic, long term action

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Synaptic Transmission

• Inhibition
• Similar to how opening Na channels allows the
  nerve to depolarize towards threshold, inhibitory
  channels allow negative ions to enter and
  hyperpolarize the cell, moving potential farther
  away from the threshold.
• Usually opens Cl- channels
• GABA, Serotonin (5-HT), etc.

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Synaptic Transmission

• Excitory Post- Inhibitory Post-Synaptic
  Potential Synaptic Potential
• EPSP IPSP

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Synaptic Transmission

• Excitatory and Inhibitory Inputs
• Sum spatially and temporally.
• Many thousands of inputs usually necessary to
  reach threshold.

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Action Potential

• Conduction Velocity
• The larger, the faster!
• lt 1 m/s for small, unmyelinated neurons
• gt 50 m/s in large myelinated neurons

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Myelin

• Conduction can be speeded by myelin
• Segmented non-conductive sheath surrounding the
  neuron.
• No (few) ion channels underneath the sheath.
• High concentration of ion channels in the nodes
  between sheath segments.
• AP jumps from one node to the next, bypassing
  propagation delays (known as saltatory
  conduction).
• Can speed conduction by 100x.

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Myelin

• Schwann Cells in PNS
• Tightly wrapped around axon.
• Each segment about 1 mm, no ion channels.
• Nodes of Ranvier in between.

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Myelin

• Oligodendrocytes in CNS
• Each cell wraps several nerves.
• More compact than individual Schwann cells.
• Also segmented with nodes.

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Postsynaptic Effects

• Three main types of effects
• Direct effect on ionic channels
• Second messenger systems
• Direct gene activation

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Postsynaptic Effects

• Direct effect on ionic channels
• Neurotransmitter binds to receptor channel
  causing a conformational change which opens the
  channel to allow the ion to pass.
• Quickest acting and shortest acting effect.
• Neurotransmitter remains in synapse and is
  metabolized or reuptaken.

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Postsynaptic Effects

• Second messenger systems
• A guanine sensitive protein (G-protein) is linked
  to the receptor.
• Neurotransmitter binds to receptor channel
  causing G-protein to activate a catalytic enzyme
  in the membrane.
• The enzyme produces a second messenger.
• The 2nd messenger can affect other receptors or
  can directly influence protein synthesis.
• Effects are slower, but longer lasting.

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cAMP Second Messenger
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Second Messengers

• The most common 2nd messengers are
• Cyclic Adenosine Monophosphate (cAMP)
• Inositol Triphosphate (IP3)
• Diacylglyceride
• 2nd Messengers
• AMPLIFICATION
• PROLONGED EFFECT

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Direct Gene Activation

• Primarily lipid-soluable steroids
• Pass through the cell and nuclear membranes.
• Led to DNA by chaperonin-receptor complexes.
• Receptor binds to acceptors on chromatin.
• Transcription of specified protein begins.
• mRNA goes to rough ER for protein synthesis.

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Neurotransmitters

• Trigger postsynaptic nerves
• Major classes of neurotransmitters
• Amino Acids
• Monoamines
• Acetylcholine
• Soluable Gasses
• Peptides
• Steroids

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Neurotransmitters

• Amino Acids
• Aspartate
• GABA (gamma aminobutyric acid) (inhibitory)
• Glutamate (excitatory)
• Glycine
• Only found in CNS

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Neurotransmitters

• Monoamines
• Synthesized from amino acids
• Catecholamines
• Tyrosine dopamine (D, DA), norepinephrine (NE),
  epinephrine (E)
• Indolamines
• Tryptophan serotonin (5-HT), melatonin
• Histidine histamine (H)
• Widely active in brain
• Imbalances associated with mental disorders

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Neurotransmitters

• Acetylcholine
• First neurotransmitter discovered
• CNS and all neuro-muscular junctions
• Soluable gasses
• NO, CO
• Peptides
• Substance P, endorphins and enkephalins (pain)
• Steroids
• Derived from cholesterol (sex)

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Neurotransmitters
DA 5-HT
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Neurotransmitters
NE GABA