Transcript Neuron Function 2

Neuron Function 2
Neuronal Cytoskeleton
The neuronal cytoskeleton is quite
important
Maintenance of shape
Normal neuronal metabolism
Nerve terminals (axonal buds) are nurtured
by materials that travel from cell body to
terminals by axoplasmic flow
Neuronal Cytoskeleton 2
Two prominent cytoskeletal elements
Microtubules
Neurofilaments- specific type of intermediate
filaments (10 nm diameter)
Both are extensively cross-linked to one
another
Neuronal Cytoskeleton 3
Actin microfilaments are also present
Actin is localized immediately adjacent to PM
Actin is also localized at the tip of growth
cones of formative neurites in development
Nerve Terminals
Axoplasmic flow is the means by which
the distant nerve terminals synaptic knobs
are bulbs are nurtured
The cell body of the cell contains the
biosynthetic machinery of the cell
The cytoskeleton is used to mediate transit of
secretory materials out to terminals and move
materials back to soma or cell body
Axoplasmic flow
Two general types
Fast 250 to 400 mm/day; typically involves
preassembly of components into membrane
bound organelle or vesicle
Slow 50 mm/day; cytoskeletal and
cytoplasmic elements (non-membrane bound)
Anterograde vs Retrograde
Axoplasmic flow is bidirectional
Anterograde is towards synaptic knob
Retrograde is back toward soma
Transit is mediated by motor proteins that
hydrolyze ATP and “walk” along the
microtuble or microfilament
Motor Proteins
Kinesin - walks toward + end (away from
the cell body towards synaptic knobs)
Cytoplasmic dynein - walks toward - end (
towards the cell body and away from the
synaptic knob)
Myosin 1 is a microfilament motor that
walks at the periphery where actin
microfilaments are prevalent
The synapse
The synapse is the narrow space that
separates an axon buton or synaptic bulb
from the soma or dendrite of a second
neuron
Two basic types of synapses
Electrical synapse - rare found only in a few
places in the body
Chemical synapse - most frequently found
type
Electrical synapses
Gap junctions connect the presynaptic
axon terminal to the postsynaptic neuron
dendrite or cell body (soma)
Individual protein subunits connexins
Six together make a pore connexon
Cells electrically connected; thus AP
passes from one directly onto the next
Chemical synapses
A narrow gap of around 20-40 nm exists
between pre and post-synaptic membrane
To transfer the signal of an arriving AP the
synaptic knob (axon terminal) releases
small molecules called neurotransmitters
into the gap
The NT’s diffuse across the gap
NT’s bind to receptors in the post-synaptic
membrane triggering a graded response
Neurotransmitters
Many different types of molecules act as
neurotransmitters
Binding to receptor turns the receptor form
off state to on
Excitatory NTs- cause depolarization
Inhibitory NTs - cause hyperpolarization
Types of
neurotransmitters
Acetyl Choline - synthesized from acetyl
CoA + choline
Most common outside CNS -cholinergic
Biogenic Amines- adrenergic
CatecholaminesEpinephrine
Norepinephrine
Dopamine
Types of
neurotransmitters
Indoleamines
5-OH tryptamine or serotonin
Histamine
Neurotransmitters 2
Amino acids
Excitatory
Aspartic
Glutamic
Inhibitory
GABA (gamma aminobutryic acid) Brain
Glycine spinal cord
Neurotransmitters 3
Peptides
Enkephalins - methionine and leucine
enkephalins (met and leu enkephalins)
Endorphins a and b endorphins
Substance P
Neurohormones
There are over 50 peptides that may be
neurotransmitters or neuromodulators
Neuropeptides
Excite, inhibit, or modify activity of other
neurons in the brain
Differ from other NTs in that they tend to
act on groups of neurons and have a long
lasting effect
Gut-Brain Neuropeptides
Excite, inhibit, or modify activity of other
neurons in the brain
Differ from other NTs in that they tend to
act on groups of neurons and have a long
lasting effect
Neurotransmitter
Receptors
Acetylcholine receptor fig 2-30 p 47
Binds two molecules of acetylcholine
MW of multmeric complex 300,000
Subunit makeup a2,bgd
Each subunit has about 500 amino acids
GABA receptor
Causes hyperpolarization by allowing Clions into the cell
GABA is an inhibitory PSP
Synapse
Cholinergic
neurotransmission
1. An arriving action potential depolarizes the
synaptic knob
2. Ca+2 ions enter the cytoplasm of the synaptic
knob.
3. ACh release occurs through diffusion and
exocytosis of neurotransmitter vesicles
4. ACh diffuses across the synaptic cleft and binds to
receptors on the postsynaptic membrane.
Cholinergic
neurotransmission 2
5. Chemically regulated sodium channels on the
post synaptic surface are activated, producing a
graded depolarization.
6. ACh release ceases because calcium ions are
removed from the cytoplasm of the synaptic knob.
7. The depolarization ends as ACh is broken
down into acetate and choline by ACh esterase.
8. The synaptic knob reabsorbs choline from the
synaptic cleft and uses it to re-synthesize ACh.
Synthesis Acetyl choline
Choline + acetyl CoA --> Acetylcholine +
CoA
Enzyme choline acetyl transferase
Inactivation of acetyl choline
enzyme acetylcholine esterase breaks down
acetylcholine to acetic acid plus choline
The acetic acid is excreted and the choline is
recycled back into the presynaptic knob of the
neuron
Adrenergic
neurotransmission
1. Arriving potential depolarizes synaptic knob
2. Ca+2 ions enter cytoplasm triggering release of
catecholamines
3. Catecholamines diffuse across the synaptic
cleft and bind to receptors in post-synaptic
membrane
4. Complex of catecholamines + receptor protein
+ adenylate cyclase produce second message
inside cytosol; namely cAMP
Adrenergic
neurotransmission 2
5. cAMP (second message) activates chemically
regulated Na+ ion channels
6. Phosphodiesterase breaks down cAMP ----->
AMP
7. Catecholamines decrease due to enzymatic
breakdown. Example: monoamine oxidase (MAO)
and Catechol-O-methyl transferase