Synapses 4 Flashcards
neuromuscular junction
Synapse between neurons of the spinal cord + skeletal muscle
Brain & NS tell muscles when to contract
An Action Potential in the motor axon ALWAYS causes an Action Potential on the muscle cell it innervates due to:
large size of synapse
large # of active zones on the presynaptic terminal
shallow folds on postsynaptic membrane, called motor end-plate creates large surface area with many receptors
mechanisms of neurotransmitter release
Vesicles dumped by exocytosis - stimulated by influx of extracellular calcium, [Ca2+] through voltage-gated Ca++ channel
Vesicle membrane incorporated into presynaptic membrane
Neurotransmitter released
Vesicle re-formed by endocytosis
types of neurotransmitters
amino acids, amines, peptides
amino acids
Small organic molecules
e.g., Glutamate, Glycine, GABA
Released from synaptic vesicles (smaller)
amines
Small organic molecules
e.g., Dopamine, Acetylcholine, Histamine
Released from synaptic vesicles (smaller)
peptides
Short amino acid chains (i.e. proteins) stored in and released from secretory granules
e.g., Dynorphin, Enkephalins, endorphins
Released from secretory granules (larger)
synthesizing amino acids and amines
Synthesizing enzymes are transported down to the axon terminal.
Once there, they synthesize the amine and amino acid NTs in the cytosol of the axon terminal.
Then special proteins called transporters that are embedded in the synaptic vesicle membrane are responsible for concentrating the NTs within the synaptic vesicles.
synthesizing peptides
Synthesized in the rough ER, then sent to Golgi Body.
At Golgi body, protein is split into peptides which are concentrated in secretory granules, which then bud off from the Golgi body and move down the axon via anterograde transport to axon terminal.
Mechanism for Amino Acids and Amines neurotransmitter release:
- Synaptic vesicles docked at active zone
- Action Potential reaches axon terminal causing voltage-gated calcium channels to open at the active zone; Ca2+ flows from outside cell to inside, down their concentration gradient
- Influx of Ca2+ stimulates exocytosis - vesicle membrane gets incorporated into presynaptic membrane and neurotransmitters released
- Vesicle is re-formed by endocytosis and refilled with neurotransmitters
Mechanism for Peptides neurotransmitter release:
- Secretory granules not located at active sites and therefore not close to influx of Ca2+
For exocytosis of granules to occur, requires series of high frequency of action potentials to elevate Ca2+ levels in the axon terminal to a high enough level to trigger release.
Release of Peptides BLANK than release of amino acids and amines.
slower
transmitter gated ion channels
neurotransmitter receptor on postsynaptic cell
Membrane-spanning proteins that change shape when NT attached
Directly allow ions through membrane
If Na+, will excite postsynaptic neuron; If K+ or Cl-, will inhibit
Transmitter-gated ion channels (con’t)
If excitatory, depolarization causes excitatory postsynaptic potential (EPSP) → ACh, Glu
If inhibitory, hyperpolarization causes inhibitory postsynaptic potential (IPSP) → Gly, GABA
g protein coupled receptors
Slower, longer-lasting actions
neurotransmitter receptor on postsynaptic cell
g coupled protein receptors steps
a) NT molecule binds to receptor proteins on postsynaptic membrane
b) Receptors activate G-protein, which crawls along inside of membrane
c) G-protein activates “effector” protein, which might:
- Open a G-protein-gated ion channel OR
- Synthesize a second messenger to initiate other tasks within the cell
excess neurotransmitter
If NTs not taken up, AP will continue out of control
If NTs left in neuromuscular junction, receptors desensitize (close), muscles fail
how to prevent excess neurotransmitter
Some taken back into presynaptic terminal
Some diffuses away
Some taken in by glia (yay glia!)
Some broken down in cleft by enzymes
autoreceptors
Neurotransmitter receptors in the Presynaptic neuron that respond to neurotransmitters released by the presynaptic terminal.
Typically G-protein-coupled receptor
Second messengers typically stop more neurotransmitter release or end the synthesis of neurotransmitters.
Way to regulate and prevent too much neurotransmitter released into the cleft.
Processes for Neurotransmitter Removal:
Some sucked back into presynaptic terminal by transporter proteins in the presynaptic membrane (reuptake), then enzymatically destroyed or put back into vesicles.
Some diffuse away from synapse
Some taken in by glia by transporter proteins in their membranes and then broken down by enzymes.
Some broken down in cleft by enzymes
If neurotransmitters left in neuromuscular junction, receptors desensitize (channels close), muscles fail
neuropharmacology
The study of the effects of drugs on nervous system tissue
Receptor agonists:
Mimic actions of naturally occurring neurotransmitters
Nicotine
binds to and activates (nicotinic) Ach receptors in skeletal muscle and in the CNS (addiction)
receptor agonist
Receptor antagonists:
bind to the receptors and block normal action of the neurotransmitter (Inhibitors)
Curare
blocks nicotinic ACh receptors causing weakness of muscles or asphyxiation due to paralysis of diaphragm (arrow poison used by South American indigenous people)
Defective neurotransmission:
Root cause of neurological and psychiatric disorders
Black Widow venom
Latrotoxin triggers ACh, norepinephrine, and GABA release until runs out; works by causing influx of Ca2+ which stimulates exocytosis – muscle cramping, rigidity, pain, stomach cramps, vomiting, sweating and fast pulse
Taiwanese Cobra venom
Cobratoxin peptide binds to ACh receptors, blocking the signal to muscles, days to be remove - paralyzes diaphragm so can cause death, chest discomfort and difficulty breathing, fever, difficulty swallowing, weak limbs
Botulinum
Clostridium botulinum bacterium that causes botulism (from poor canning)
Prevents docking of vesicles with ACh so blocks release of ACh into the synapse – respiratory muscle paralysis can cause death
If transmitter gated ion channel allows Na+ to enter, then
Na+ flow into the postsynaptic neuron causing depolarization and a graded potential flows to the axon hillock which can help trigger an action potential.
If transmitter gated ion channel allows Cl- to enter, then
Cl- flows into the postsynaptic neuron causing hyperpolarization, decreasing the chance the cell will fire an action potential. (hyperpolarization can occur from K+ flowing out of cell.)
na+
depolarize the postsynaptic membrane causing it to reach threshold
Excitatory Post-Synaptic Potential (EPSP)
cl-
hyperpolarize the postsynaptic membrane
Inhibitory Post-Synaptic Potential (IPSP)
If excitatory, depolarization causes
If inhibitory, hyperpolarization causes
excitatory postsynaptic potential (EPSP) → ACh, Glu
inhibitory postsynaptic potential (IPSP) → Gly, GABA
Neural Integration
– combining the signals coming from the synapses to get a net change in membrane potential at the Axon Hillock.
after synaptic transmission
