Two types of signal conduction within a single neuron

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• Two types of signal conduction within a single
  neuron
• Passive (graded) electrotonic conduction depend
  on the movement of ions along the two faces of
  the plasma membrane decays with distance.
• Active (regenerative) conduction (AP) depend on
  the presence and activity of biological molecules
  such as voltage-gated ion channels transmit
  without loss of signal strength.

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• Passive electrotonic conduction decays with
  distance
• Cytoplasm resistance
• Plasma membrane resistance
• Charges leaks out

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Length constant (?) is defined as the distance
over which a steady-state potential shows a 63
drop in amplitude.
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• Propagation of a nerve impulse (AP) along the
  axon depends on
• The passive cable properties of an axon.
• The electrical excitability of Na channels in
  the axon membranes.

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• Increasing conduction velocity of AP
• Increase axonal diameter
• Myelination

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Conduction in Myelinated Axon

• Myelin prevents movement of Na and K through
  the membrane.
• Nodes of Ranvier contain VG Na and K channels.
• Saltatory conduction (leaps).
• Fast rate of conduction.

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Nodes of Ranvier One of the regularly spaced
interruptions of myelin sheath along an axon.
Saltatory conduction Discontinuous conduction of
action potentials that takes place at the nodes
of Ranvier in myelinated axons.
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Synapse

• Functional connection between a neuron and
  another cell.
• Different types of synapses involve
• Axodendritic (b)
• Axon of one neuron and dendrite of another
  neuron.
• Axosomatic (a)
• Axon of one neuron and cell body of another
  neuron.
• Axoaxonic (c)
• Axon of 1 neuron and axon of another neuron.
• Transmission in one direction only.

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• Two types of synapses for transmit
  information between neurons
• Electrical synapse
• Chemical synapse

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Electrical synapses
At electrical synapses, the presynaptic cell and
postsynaptic cell are connected by protein
complexes called gap junctions, which are made of
of subunits called connexins.
Electrical synapses provide rapid and faithful
signal transmission between cells, but a less
flexible response than chemical synapses.
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Electrical Synapse

• Impulses can be regenerated without interruption
  in adjacent cells.
• Gap junctions
• Adjacent cells electrically coupled through a
  channel.
• Examples
• Smooth and cardiac muscle.
• CNS, retina

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Chemical Synapse

• Presynaptic terminal (bouton) releases a
  chemical (neurotransmitter).
• Synaptic transmission is through a chemical gated
  channel.

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Chemical Synapse

• Terminal bouton is separated from postsynaptic
  cell by synaptic cleft.
• Neurotransmitters (NT) are released from synaptic
  vesicles.
• Amount of neurotransmitter released depends upon
  frequency of AP.

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Synaptic Transmission

• AP travels down axon to bouton.
• VG Ca channels open.
• Ca enters bouton down concentration gradient.
• Ca activates calmodulin, which activates
  protein kinase.

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Synaptic Transmission

• NT is released and diffuses across synaptic
  cleft.
• Neurotransmitter (ligand) binds to receptor in
  postsynaptic cell.
• Chemical gated ion channel opens.
• EPSP depolarization.
• IPSP hyperpolarization.
• Neurotransmitter inactivated.

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Chemical synapses
Signals are carried across the synaptic cleft
between the presynaptic and postsynaptic cells by
the diffusion of neurotransmitter molecules.
Fast direct chemical synapses the transmitter
receptor proteins include the both the binding
site for the transmitter and an ion channel.
Neurotransmitters are synthesized in the axon
terminals and stored in small vesicles. These
transmitters are typically small organic
molecules.
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Slow indirect chemical synapses the transmitter
receptor proteins act through intracellular
messenger systems to affect the conductance
through ion channels. The transmitters are
typically large molecules containing a single
amino acid (biogenic amines) or several amino
acid residues (neuropeptide). They are usually
synthesized in the soma, packaged into large
vesicles, and transported to the axon terminal.
The onset of response is slower, but last longer
(seconds to hours)
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Excitatory postsynaptic potential (epsp) A change
in the membrane potential of a postsynaptic cell
that increases the probability of an action
potential in that cell. Inhibitory postsynaptic
potential (ipsp) A change in the transmembrane
potential of a postsynaptic cell that reduces the
probability of an action potential in that cell.
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Excitatory postsynaptic potential (epsp) The
current are typically carried through Na or
Ca2. Inhibitory postsynaptic potential (ipsp)
The current are typically carried through
channels that are permeable either to K or to
Cl-.
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Synaptic Integration

• EPSPS can summate, producing AP.
• Spatial summation
• Numerous boutons converge on a single
  postsynaptic neuron (distance).
• Temporal summation
• Successive waves of neurotransmitter release
  (time).

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EPSP

• No threshold.
• Decrease resting membrane potential.
• Closer to threshold.
• Graded in magnitude.
• Have no refractory period.
• Can summate.

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IPSP

• No threshold.
• Hyperpolarize postsynaptic membrane.
• Increase membrane potential
• Further away from threshold.
• Can summate.
• No refractory period.

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Excitation and inhibition depend critically on
the nature of the local ionic gradients
(properties of the channel identities of the
ions that flow) and not on the identity of the
signaling molecule.
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• Presynaptic inhibition Neuronal inhibition
  resulting from action of an inhibitory terminal
  that synapses on the presynaptic terminal of an
  excitatory synapse, which reduces the amount of
  transmitter released.
• Increasing gk and gCl in the presynaptic
  terminals
• Reducing Ca2 entry in the presynaptic terminals

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• Neurotransmitter releasing depends on
• Depolarization of presynaptic membrane
• More depolarization caused more transmitter to be
  released
• Extracellular Ca2 concentrations

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• Transmitter release steps
• Mature vesicles move up to active zones with
  assistance of cytoskeletal protein actin and
  myosin.
• Vesicle attached to membrane by the sec6/8 and
  rab proteins (reversible)
• Attached irreversibly by forming SNARE complex
• Synaptotagmin interacts with the SNARE complex to
  produce rapid fusion.

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Classification of neurotransmitters

• Acetylcholine (ACh)
• Biogenic amines (norepinephrine, dopamine,
  serotonin, histamine)
• Amino acids (r-aminobutyric acid, glutamate,
  glycine)
• polypeptides (somatostatin, substance P, LHRH)
• Novel messengers (ATP, NO, CO)

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Acetylcholine (ACh) as Neurotransmitter

• ACh is both an excitatory and inhibitory NT.
• Causes the opening/closing of chemical gated ion
  channels.

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Ligand-Operated ACh Channels

• Most direct mechanism.
• Ion channel runs through receptor.
• Receptor has 5 polypeptide subunits that enclose
  ion channel.
• 2 subunits contain ACh binding sites.
• Permits diffusion of Na.

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G Protein-Operated ACh Channel

• Only 1 subunit.
• Ion channels are separate proteins located away
  from the receptors.
• Binding of ACh activates alpha G protein subunit.
• Alpha subunit or the beta-gamma complex diffuses
  through membrane until it binds to ion channel,
  opening it.

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• General events at G-protein coupled receptor
• Neurotransmitter binds to the receptor protein
• GDP is released from Ga subunit
• GTP binds to the a protein cause dissociation of
  G-protein from the receptor and bg from a
  subunits
• Activated a subunit, or the beta-gama complex
  binds to the effector molecules (signal
  transduction)
• GTP was hydrolyzed to GDP by GTPase (termination
  of signal)
• Bound to GDP again, the a and bg form complex and
  bind to the receptor.

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• At least three separate proteins contribute to
  slow, indirect
• chemical synaptic transmission
• Neurotransmitter receptor protein (seven
  transmembrane domains)
• Activated G proteins including a subunits or bg
  comlex,
• Effector proteins (ion channels, enzyme for 2nd
  messenger)

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• G-proteins can function only if GTP is available
• Nonhyrolyzable analog of GTP, GTPgS induce stable
  activation of
• the Ga protein.

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Acetylcholinesterase

• AChE
• Enzyme that inactivates ACh.
• Prevents continued stimulation.

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Monoamines as NT

• Monoamine NTs
• Epinephrine
• Norepinephrine
• Serotonin
• Dopamine
• Released by exocytosis from presynaptic vesicles.
• Diffuse across the synaptic cleft.
• Interact with specific receptors in postsynaptic
  membrane.

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Mechanism of Action

• Monoamine NT do not directly open ion channels.
• Act through second messenger, cAMP.
• Binding of norepinephrine stimulates dissociation
  of G protein alpha subunit.
• Alpha subunit binds to adenylate cyclase,
  converting ATP to cAMP.
• cAMP activates protein kinase, phosphorylating
  other proteins.

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• Reuptake of monoamines into presynaptic membrane.
• Enzymatic degradation in presynaptic membrane by
  MAO.
• Enzymatic degradation in postsynaptic membrane by
  COMT.