3 - Synaptic Transmission Flashcards
How many chemical synapses does a typical CNS neuron fire or receive?
Tens of thousands
Synaptic steps broken down
Presynaptic action potential reaches terminus
Ca2+ is released in the bouton
Neurotransmitter is exocytosed into synaptic cleft
Neurotransmitter activates postsynaptic receptors
Postsynaptic action potential (excitatory) is produced
Two types of chemical synaptic receptors
Ionotropic Receptors
Metabotropic Receptors
Ionotropic Receptors
Ligand-gated ion channels.
Binding of neurotransmitter induces conformational change, opening ion channel pore, allowing influx or efflux of ions, leading to membrane depolarization or hyperpolarization
Metabotropic Receptors
Trigger 2nd messengers regulating ion channel activity indirectly.
Ionotropic Receptors - Speed, Effect, Location
Fast (milliseconds)
Excitatory or Inhibitory
Localized within synapse
Metabotropic Receptors - Speed, Effect, Location
Slow (hundreds of milliseconds - seconds - minutes)
Regulate excitability of postsynaptic neurons (alters resting membrane potential, or duration/threshold of postsynaptic action potential)
Homosynaptic Plasticity???
The activity of the nerve terminal itself can alter release properties at the synapse
Heterosynaptic Plasticity
Modulatory neuron releases modulatory neurotransmitter onto presynaptic nerve terminal.
Types of Heterosynaptic Plasticity
Presynaptic Inhibition
Presynaptic Faciliation
Presynaptic Facilitation
Modulatory neurotransmitter inhibits presynaptic K+ channels, prolonging the action potential.
Neuromuscular Junction Synapse - Steps
Motor Neuron release Acetyl Choline
Acetyl Choline activates Nicotinic Acetyl Choline receptors on postsynaptic membrane (muscle)
Curare
Poison on the heads of arrows in Central and South America.
Binds nicotinic Acetylcholine receptors (competitive inhibition)
Reduces excitatory action potential depolarization
No muscle contraction
Asphyxia (diaphragmatic paralysis)
Nicotinic ACh Receptor
Ligand gated cation channel, permeable to most cations (Na+, K+, Ca++)
Predominantly drives cations in.
Depolarization.
Excitatory action potential.
Nicotinic ACh Receptor - Structure
Pentameric membrane protein
Composed of 4 Homolygous subunits (Delta, Beta, Gamma, two Alpha) - each with 4 transmembrane domains and an extracellular N & C terminus
Myasthenia Gravis
Autoimmune
Ab bind Nicotinic ACh receptors, reducing density of expression of Nicotinic receptors on surface
Leads to muscle weakness
Congenital Myasthenic Syndrome
Genetic mutation in Nicotinic ACh Receptor in neuromuscular junction
Stretch Reflex Circuit (Extensor as an example)
Extensor muscle spindle sensory neuron activated by stretch
Releases glutamate onto extensor motor neuron within spinal cord.
Excitatory postsynaptic action potential leads to muscle contraction
Glutamate
Excitatory neurotransmitter
Inhibitory Circuit (When Extensor is stretched)
Muscle spindle afferent nerve fibers synapse on inhibitory interneurons.
These fire an inhibitory action potential on the Flexor muscle
Neuromuscular Junction Excitatory Neurotransmitter
Acetylcholine
Spinal Cord Excitatory Neurotransmitter
Glutamate
Inhibitory Neurotransmitters (Interneurons)
Gamma-Aminobutyric Acid (GABA)
Glycine
Activation of GABA or Glycine receptors leads to
Hyperpolarization of the cell membrane (preventing action potentials from firing)
2 Classes of Ligand-Gated Ionotropic Receptors
GABA/Glycine receptors
GABA-A & Glycine Receptors
Antimeric
Permeable to Cl-
Allows Cl- influx
Leads to Membrane Hyperpolarization
Nicotinic Acetylcholine Receptors
Antimeric
Excitatory
Similar to GABA/Glycine, but not permeable to Cl-
Which drugs act through the GABA receptor, increasing and prolonging duration of inhibitory currents, and enhanced hyperpolarization?
Barbituates
Benzodiazepines
Alcohol
General Anesthetics
Glutamate Receptors
Tetramer (Distantly related to K+ Channels)
3 Transmembrane Domains per subunit
Extracellular N-Terminus
Intracellular C-Terminus
3 Families of Ionotropic Glutamate Receptors
AMPA Receptor (non-NMDA) Kainate Receptor (non-NMDA) NMDA
AMPA Receptor
Permeable to Na+, K+
Channel opened by binding of Glutamate molecule
Located in Postsynaptic Membrane Surfaces
Responsible for fast glutamatergic response
Kainate Receptor
Permeable to Na+, K+
Channel opened by binding of Glutamate molecule
Located in Presynaptic terminal
NMDA
Permeable to Na+, K+
High Ca++ Permeability
Channel opened by binding of 2 Glutamate & 1 Glycine
There is enough Glycine in CSF, though, that functionally, these channels depend more on Glutamate release
Mg++ can plug ion channel pore, blocking ion flux, even when channel is open.
Depolarization evicts the Mg2+.
Effectively, NMDA receptors respond to the combination of ligands AND voltage.
Located on postsynaptic membrane surface
PCP (Angel Dust) can lead to NMDA hyperfunction.
AMPA vs NMDA
AMPA action potentials rise and fall more quickly
NMDA rises and falls more quickly
At further depolarized states, Mg++ is not an issue anymore, so NMDA is more active.
Long Term Depression (With respect to synapses)
AMPA receptors removed from postsynaptic membrane surface
