Transcript Neurotransmitter Types

Neurotransmitter Types
Scanned from Squires et. al.
Fundamental Neuroscience
Patton’s Requirements for
Neurotransmitters
• 1 Neurotransmitters must be synthesized in
the presynaptic neuron: in the cell body and
transmitted to the terminal end button or
synthesized within the terminal end button.
• 2 The substance should be released from the
nerve terminals in a chemicallypharmacologically identifiable form.
• 3 A neurotransmitter should reproduce at the
postsynaptic cell the specific events (such as
changes in membrane properties) that are
seen after stimulation of the presynaptic
neuron.
• 4 (A) The effects of a putative
neurotransmitter should be blocked by
competitive antagonists of the receptor for
the transmitter in a dose dependent manner.
• (B) Treatments that inhibit synthesis of the
transmitter should block the effects of
presynaptic stimulation
• 5. There should be active mechanisms to
terminate the action of the putative
neurotransmitter (uptake by the presynaptic
neuron or glial cells through specific transport
mechanisms, or enzymatic inactivation of the
chemical messenger).
Two Large Categories of
Neurotransmitters
• Traditional
• Nontraditional
GABA synapse
Nontraditional synapses
• Peptide synapses
• Nitric oxide (the gas)
Peptide synapse
Nitric Oxide
Ionotrophic synapses
• nACh receptor is opened by ACH, such that all
small ions (Na+, K+, Cl-) run down their
diffusion gradiant.
Metatrophic
• Neurotransmitter opens gates if coupled with
G proteins.
Acetylcholine neuromuscular
Junction
• At the end of the 1930s and early 40s the
general conclusion was reached that the first
post synaptic event was a negative going
depolarization of the muscle fiber.
• Named the end-plate potential
• Was restricted to the end-plate region.
• Is sufficient in size to generate and actionpotential which propagates the length of the
fiber.
Acetylcholine
• Dale investigated a substance obtained from
ergot a fungal infection of cereal.
• Slowed heart rate of the cat, and lowered
blood pressure.
• Hypothesized that acetylcholine occurred
naturally in the body and hydrolized by an
enzyme in the body accounting for the
inpossabillity of it being isolate in from the
body.
Lowe’s study on frog heart
• Found that stimulation of the Vagus nerve
caused heart1 to lengthen the beat to beat
time frame slowing heart rate.
• An aliquot of the perfusion fluid of heart1
when transfered to heart 2, with no
stimulation of heart2’s Vagus nerve caused
heart 2 lengthen its beat to beat time frame
and slow heart 2 down.
Dale and Dudley’s study
• Isolated acetylcholine from the spleen of cows
and horses.
• Demonstration that acetylcholine could be
isolated from the ganglia of the sympathetic
nervous system and at nerve terminals in the
motor muscles of the sckelatal. system
Construction-Destruction
• Construction
• Acetyl Co A + choline == Acetylcholine
• Destruction
• Acetylcholine + acetylcholinesterase ==
•
choline + acetic acid
Drawing the neural endplate and
underlying muscle
Legend for previous slide
Fatt and Katz study
Arrangement for Intracellular recording of post
synaptic neuromuscular junction
Using the apparatus from the previous slide for Intracellular recording of post
synaptic neuromuscular junction. The electrode is rode is progressively move
away from the axon in mm steps
Voltage clamp
Results of voltage clamp study
Electrical stimulation of the axon of the presynaptic
membrane is different in from direct stimulation of the
muscle fiber.
Iontophertic injections of Ach, developed by Nastuk
(1953) further developed by Katz and del Catillo (1955)
del Castillo and Katz study results
Miniature end-plate potentials
• In the resting membrane, small potentials of
about 0.5mV can be recorded.
• Could only be found at the end-plate in
curarized preparations.
• Could not be found in preparations where the
muscle had been previously denervated two
weeks previously.
Miniature end-plate potentials
Characteristics of the miniature
end-plate potential
• According to Katz, the frequency of the
miniature end-plate potentials is controlled by
the conditions of the presynaptic membrane,
while the amplitude is controlled by the
properties of the postsynaptic membrane
Quantal release of Acetylcholine
• A combination of Mg and Ca can be used to
block the release of ACH.
• When this concentration if used appropriately,
the size of the successive EPP will fluctuate in
a step-wize manner (see curve below).