Lecture 12: Synaptic Transmission Flashcards
How do electrical events pass from cell to cell? = 2
- Direct electrical transmission-cardiac and some types of smooth muscle
- By use of a chemical mediator - chemical synaptic transmission between nerve and muscle, nerve and nerve
What happens during Electrical Transmission at Electrical synapse?= 4
1 * <5 nm between pre- and post-synaptic membrane
2 * Transmission by ion current
3 * Virtually no synaptic delay
4 * Bidirectional
What happens during Chemical Transmission at Chemical synapse?= 4
1 * 20-40 nm between pre- and post- synaptic membrane
2 * Transmission by chemical neurotransmitter
3 * Synaptic delay (at least 0.3 ms, generally 1-5 ms, can be longer)
4 * Unidirectional
Electrical Neurotransmission: CONNEXONS
Connexons – 6 identical protein subunits; allow direct electrical transmission from cell to cell (eg cardiac muscle, some smooth muscle)
Opposing conexons on pre & post-synaptic cells – directly linking cytoplasm
What is a JUNCTION?
— In neuroscience a junction is a connection from a neuron to another cell type, i.e. a synapse
— In biochemistry a junction is a type of protein that connects cells
together e.g. tight junctions and gap junctions
Can cause a bit of confusion, e.g. there are no junctions in vertebrates formed from gap junctions.
What is A RECEPTOR?
—– In neuroscience a receptor is a sensory cell that detects some
signal and turns it into an electrical potential, e.g. touch receptors.
—-In pharmacology a receptor is protein that binds a drug, hormone or neurotransmitter, e.g. nicotinic receptors
Steps of Chemical Neurotransmission: 5
- Action potentials DEPOLARIZE the nerve terminal
- Opens voltage gate calcium channels
- Calcium enter the nerve terminal increase local calcium concentration
- Vesicle contents (neurotransmitter) are released by exocytosis
- Neurotransmitter reacts with ligand-gated channels in post- synaptic cell membrane
Calcium as a Signalling Molecule: 3
- Voltage gate Nav channels are very fast
- Voltage gated calcium channels are slower
- But Ca2+ can bind and activate proteins
- Troponin
- Calmodulin
-Calmodulin
- Synaptotagmin
Calcium as a Signalling Molecule: TROPONIN
Troponin inSKELETAL MUSCLE binds Ca2+ and causes muscle contraction.
Calcium as a Signalling Molecule: CALMODULIN
- Calmodulin in SMOOTH MUSCLE binds Ca2+ and causes muscle contraction.
- Calmodulin in STOMACH GLAND binds Ca2+ and causes acid secretion.
Calcium as a Signalling Molecule: SYNAPTOTAGMIN
Synaptotagmin in NERVES binds Ca2+ and causes neurotransmitter release
UNDERSTANDING Synaptic Vesicles = 7
- Neurotransmitters are stored in VESICLES.
- Vesicles are stacked around the ACTIVE ZONE.
- Active zone = release site vesicles - Some vesicles are almost touching the cell membrane , DOCKED VESICLES.
- Voltage gated Ca2+ channels opened by action potential.
- Entry of Ca2+
Vesicles fuse with pre-synaptic membrane.
6.Neurotransmitter released in distinct packages (vesicle = QUANTA)
7.**High density vesicles / high density Ca2+ channels
EXOCYTOSIS OF TRANSMITTER - image
- ACTIVE ZONE
- SYNAPTIC CLEFT
3.VESICLE FUSION - COATED PITS AND COATED VESICLES
Vesicle Release = procedure 5
- Readily releasable pool of vesicle (RESERVE POOL)
- “DOCKING” of vesicles at cell membrane; active zone
- A complex of SNARE (soluble NSF-attachment protein receptor) proteins docks the vesicle
- Binding of Ca2+ to SYNAPTOTAGMIN causes a conformational change in the SNARE complex
- Vesicle pulled into cell membrane producing exocytosis
UNDERSTANDING Vesicle Release and Recycling = 7
- VESICLES filled with neurotransmitter docked by SNARE proteins to ACTIVE ZONE
- An ATP dependent process is required to PRIME the vesicles for release
- Ca2+ entry allows calcium to bind SYNAPTOTAGMIN
- Triggers EXOCYTOSIS
- Some vesicles are restocked with neurotransmitter with out undocking, kiss-and-stay.
6.Some vesicles are undocked and refilled, kiss-and-run.
- Some vesicles go through ENDOCYTOSIS and reprocessed through ENDOSOMES
Neurotransmitter Criteria
“a substance that is released at a synapse by one neuron and affects another cell in a specific manner”
Neurotransmitter Criteria = 5
- Synthesised in pre-synaptic cell and stored in PRESYNAPTIC terminal
- RELEASED upon STIMULATION
- SPECIFIC RECEPTOR must exist on post-synaptic cell
- Experimental application of transmitter must mimic action of NEURAL STIMULATION.
5.INHIBITING the proposed transmitter must inhibit the normal function
Main Categories of Transmitters = 5
- simple amino acids
- Classical neurotransmitters
- Neuropeptides
- Purines and Pyrimidines
- Free radical gas
Simple amino acids = 3
- Glutamate,
- glycine, aspartate,
- GABA (g-aminobutyric acid, synthesised
from glutamate)
classical neurotransmitters = 5
- ACh (acytylcholine),
- serotonin (5-HT),
catecholamines:
- dopamine,
- adrenaline,
- noradrenaline
neuropeptides
Many eg insulin, glucagon, bradykinin, hypothalamic and pituitary
hormones etc etc
Purines and pyramidines = 3
ATP
ADENEINE
GUANINE
Free Radical gas =
NO (nitric oxide)
MULTIPLE RECEPTORS
(2)
Receptor (not just the neurotransmitter) on postsynaptic element determines postsynaptic response
- ACh: NICOTINIC (N-cholinergic) and MUSCARINIC (M-cholinergic) receptors
-
NA and Adr: a and b adrenergic receptors,
- a-adrenergic receptors contract smooth muscle,
- b-adrenergic receptors relax smooth muscle
Understanding Neuromuscular Junction or MOTOR END PLATE = 6
- Relatively simple
- Easily accessible
- “large”
- One muscle cell generally innervated by only one pre-synaptic axon (through multiple branches)
- Neurotransmitter directly opens one ion channel type.
6.Close relationship Ca2+ channels and synaptic active zone
Fate of Released Neurotransmitters =
Enzymatic degradation and reuptake of acetylcholine
— 5
- Diffusion
- Degradation in synaptic cleft
——acetylcholinesterase (ACHe) - REUPTAKE into pre-synaptic terminal
- Enzymatic destruction of reloading
- Involves transporter molecules
Autoimmune Disorders = 2
1.Lambert-Eaton syndrome
2.Myasthenia gravis
Lambert-Eaton syndrome = 3
1 * antibodies against voltage gated Ca2+ channels
2 * reduced amount of ACh released
3 * treated by decreasing ACh breakdown (eg pyridostigmine, neostigmine) or increasing calcium influx (eg 3,4-diaminopyridine)
Myasthenia gravis = 3
1 * antibodies against nicotinic ACh receptors
2 * reduced number of functional receptors
3 * reversed by inhibition of acetylcholinesterase (eg pyridostigmine, neostigmine)
Summary = 8
- A few CNS synapses are electrical, made from gap junctions like in the heart
- Most synapses are chemical and use a neurotransmitter
- The same transmitter can have different actions if the receptors
are different - Five main classes of neurotransmitter substances
- Depolarization of the nerve terminal opens voltage gated Ca2+ channels
- Calcium entry binds synaptotagmin and causes SNARE proteins to exocytose neurotransmitter
- Transmitters are stored in synaptic vesicles (except NO)
- Released transmitter is either degraded in the synaptic cleft or taken up into the pre-synaptic cells
