Lecture 19 (11a) - Cell Communication Part 1 Flashcards
(58 cards)
1
Q
Neurons communicate with other neurons or target cells at
A
synapses
2
Q
Chemical synapse
A
chemicals from a presynaptic cell induce changes in a postsynaptic cell
• 20-40nm
• neuron-neuron
• neuron-muscle
3
Q
Electrical synapse
A
the action potential spreads directly to the postsynaptic cell
• 3nm
• neuron-neuron
• cardiac-cadiac
• in vertebrates, CHEMICAL synapses are more common
4
Q
A … is a great model of a chemical synapse
A
neuromuscular junction
5
Q
Neuromuscular junctions
A
• chemical synapses between motor neurons and skeletal muscle cells
6
Q
In all vertebrate neuromuscular junctions, the neurotransmitter is
A
acetylcholine (ACh)
7
Q
Motor neurons have
A
1 axon (as usual) and finishes into many terminals
8
Q
Motor unit
A
1 motor unit connected to 1 muscle
9
Q
Motor axon terminal
A
- presynaptic terminal
* full of ACh
10
Q
Motor end plate
A
depression in muscle membane
• terminal of motor neuron sits in depression
11
Q
Ach is made
A
- in the cell body
- packaged into vesicle by golgi
- transported
- released through exocytosis
12
Q
ACh released through exocytosis
A
vesicle fuses with presynaptic at axon terminal
13
Q
Synaptic cleft
A
space between presynaptic and postsynaptic membranes
• 20-40 nm
14
Q
In a mammalian neuron, ion concentrations
A
outside more (+) inside more (-) • Na+ moves in, K+ moves out • more Na+ moves in than K+ moves out = depolarized • Ca2+ more out than in = moves in
15
Q
K+ ion concentration (mM)
A
intracellular = 140 extracellular = 5
16
Q
Na+ ion concentration (mM)
A
intracellular = 10 extracellular = 145
17
Q
Cl- ion concentration (mM)
A
intracellular = 20 extracellular = 110
18
Q
How is the electrical signal (action potential) transmitted to another cell
A
- an action potential causes voltage Na+ channels to open
• the depolarization causes voltage-gated Ca2+ channels to open - Ca2+ enters the axon terminal
- Ca2+ triggers fusion of acetylcholine vesicles w/ the presynaptic membrane
• SNARE complex proteins - vesicles release ACh into the synaptic cleft by exocytosis, then ACh diffuses across the synaptic cleft to the motor end plate of the muscle cell
19
Q
SNARE is sensitive to
A
Ca2+
• change configuration, can act on vesicle to fuse to presynaptic
20
Q
Thomas Sudhof
A
- Medical or physiology Nobel Prize 2013
- awarded for his work on how neurotransmitter is released at the presynaptic junction
- he identified molecular machinery that responds to an influx of calcium ions and directs neighbor proteins rapidly to bind vesicles to the outer membrane of the nerve cell
21
Q
Synaptic function involves hundreds of proteins
A
- vesicle formation
- transport of neurotransmitter into vesicles anchoring of vesicles of cytoskeletal elements
- docking of the vesicles with the presynaptic membrane
- fusion of the vesicular and cell membranes
- endocytosis of the vesicle membrane for recycling
- synaptic function = release of ACh
- vesicle formatted in golgi
22
Q
Some of these proteins are targets for
A
toxins
• the botulinum toxin and tetanus toxin
• act on a protein that is required for vesicle fusion
• BLOCKS RELEASE OF ACH AT THE NEUROMUSCULAR JUNCTION
• these toxins are responsible for Botulism and the tetanus (impairs muscle contraction, respiratory failure)
23
Q
Voltage-gated channels
A
responds to change in voltage across a membrane
24
Q
Chemically-gated channels
A
depend on specific moleucles that bind or alter the channel protein
25
Mechanically-gated channels
respond to force applied to membrane
26
Chemical synaptic transmission begins with the
arrival of an action potential
• receptor is chemically sensitive
(Na+ voltage channel at bottom of postsynaptic membrane)
• ACh lets Na and K through
(electrochemical gradient favors Na in)
• reaches top of postsynaptic, spreads down to voltage Na+ channel mainly (a little K+ also)
27
Acetylcholine moelcules diffuse
* ACh molecules diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane
* when receptors bind, they open their cation channels (Na+ and K+) and depolarize the postsynaptic membrane
* the spreading depolarization fires an action potential in the postsynaptic membrane
28
Synapses between motor neurons and muscle cells are
excitatory
| • ACh always causes depolarization
29
Other synapses can be inhibitory if
the postsynaptic response is hyperpolarization
30
A neuron has many synapses
can go over 1,000
| and receive many different chemical messages
31
The 3 main neurotransmitters in the brain are amino acids
• glutamate - excitatory
• glycine - excitatory
• γ-aminobutyric acid (GABA) - inhibitory
(regulates neuronal excitement)
(and ACh always excitable at neuromuscular junction)
32
Why is GABA inhibitory?
• GABA binds to Cl- channels or K+ channels
• if those channels are opened, Cl- moves into the cell and K+ leaves the cell
• each movement of ion is hyperpolarizing
(the membrane potential becomes more negative)
• less chance for action potential if membrane is even more (-)
33
In experiments with the transgenic Down syndrome mice
with learning ability decreased
• if we give a drug that blocks the GABA receptor (antagonist) to reduce GABA's inhibitory action
will the learning ability of the mice increase?
too much inhibition (from GABA) = learning decreased
suppress inhibition (block GABA)
--> learning ability increased?
34
Hypothesis: excessive inhibition of neurons by GABA impairs the learning ability in a mouse model of Down syndrome
1. place the mouse in an arena w/ 2 objects and allow them to explore and investigate; remove mouse
2. after 24 hours, change one of the 2 objects and return the mouse to the arena; compare the amount of time the mouse spends with the old vs the novel object. If the mouse spends more time with the novel object, it remembers the old object (has "learned")
3. repeat the experiment with normal and Down syndrome mice before and after the subject mice are treated with a drug that blocks GABA receptors (GABAr)
35
Object recognition memory test
* mouse gets used to object = no longer explores
* new object = goes for new (remember what was before) = learns
* natural behavior = always explore what is new
* day 2: do you remember what you saw yesterday? if they remember, they will explore the new object, and less the one they know 50/50 is the chance level
36
Block GABA
* wild-type is the same
* DS explored more than on the first day
• bad = not that specific an experiment
37
Neurotransmitters in the brain
* monoamines - dopamine, norepinephrine, serotonin
* peptides such as endorphins and enkelphalins
* substance P
* nitric oxide
38
Serotonin
depression
39
Dopamine
reward/pleasure
40
Norepinephrine
same thing as adrenaline
41
Nitric oxide
gas at synapse
42
The action of a neurotransmitter depends on
the receptor to which it binds
• each neurotransmitter can have multiple receptor types
eg ACh as 2 and have different effects in different tissues
• nicotinic receptors - ionotropic, mainly excitatory (in neuromuscular junction and in the gut smooth muscle - depolarize and then mobility increased)
• muscarinic receptors - metabotropic, mainly inhibitory (in the cardiac muscle - hyperpolarize and then slows down)
43
Neurotransmitter receptors are in 2 categories
* ionotropic receptors
| * metabotropic receptors
44
Ionotropic receptors
ion channels
• if a neurotransmitter binds, it causes a change in ion flow
• responses are fast and short-lived
(direct action)
• can also be chemical, but mostly ions
45
Metabotropic receptors
* include signalling cascades that lead to changes in ion channels
* responses are slower and longer lived
* slower because sequence of actions
* more modulation in behavior of cell
46
Turning neurotransmitter action off is as important as turning it on
• neurotransmitters must be cleared from the synaptic cleft after release in order to stop their action
• enzymes can destroy the neurotransmitter
(eg ACh is destroyted by acetylcholinesterase AChE)
• if AChE is inhibited, ACh stays in the synaptic cleft and causs spastic muscle paralysis and death. Some nerve gasses and insecticides inhibit AChE
47
Neurotransmitter stays
in the cleft
| • must be constantly moved or spasm --> death
48
Neurotransmitters can be broken down by enzymes or can simply
diffuse away from the cleft
or be take up by active transport by glial cell membranes
eg the antidepressant Prozac slows reuptake of the neurotransmitter serotonin, thus inhancing serotonin's activity at the synapse
49
Many drugs affect synaptic interactions
* agonists
| * antagonists
50
Agonists
mimic or potentiate the effect of a neurotransmitter
• usually not from body
(eg synthesized)
51
Antagonists
block the actions of a neurotransmitter
• eg morphine is an antagonist at the endorphin receptor and blocks pain
• protein that blocks
52
Electrical synapses couple neurons electrically via
gap junctions
• presynaptic and postsynaptic membranes are only a few nanometers apart (3nm vvs 30nm for chemical synapses)
• connexins form pores that connect the cytoplasms and allow ion flow
• transmission is very fast and bidirectional
(0.2ms vs 2ms for chemical synapses
• important in cardiac muscle cels because synchrony is vital
* electrical synapse = gap junction, close, bound by protection (tunnel of a protein)
* between 2 neurons
* not in sperm - faster than chem = in heart
53
Electrical synapses are found everywhere but
are less common in vertebrates
54
Electrical synapses require
a large area of contact between the membranes
55
Depolarization always creates a
deploarization
and hyperpolarization always creates a hyperpoleraization
(non summation like in the chemical synapse)
• less complex than chemical synapses
56
Gap junctions (electrical synapses) in
cardiac muscle and smooth muscle (guts and blood vessels)
57
Gap junctions allow
cytoplasmic continuity and electrical signalling
• thanks to those gap junctions, action potentials spread rapidly, causing a large number of cardiac muscle cells to contract simultaneously
58
Heart contractions
* in the cardiac cycle, contraction and relaxation of heart is independent of any nerve stimulation
* pace maker cells are cardiac cells that initiate action potentials without stimulation to initiate its own contractions
* the other cells that are not pace maker (majority) beat (contract) because of the cell-to-cell communication via the gap junctions in the myocardial cell themselves
* heart contraction doesn't need nerves (can beat on their own when together in synchrony)
* pace makers initiate
* gap junction = rest contract too (action potential spreads)
