Flashcards in Kenyon: Synaptic Transmission Deck (66):
What allows ions to move between the cells?
Cells connected by gap junctions are (blank). They have the same (blank).
electrically coupled; membrane potential.
A depolarization in the presynaptic neuron will be conducted directly into the (blank) neuron.
T/F: The concept of “presynaptic” and “postsynaptic” may not be useful for electrical synapses. APs can go both ways.
Populations of cells may have synchronized electrical activity. Give a few examples of cells that exhibit this behavior.
particular CNS neurons **control of breathing, hormone-secreting cells in hypothalamus
Membrane bound organelles in the presynaptic terminal containing one or several different neurotransmitters.
A relatively wide space separating the pre- and post-synaptic neurons
List the steps in chemical neurotransmission.
1. transmitter is synthesized and then stored in vesicles
2. an AP invades the pre-synaptic terminal
3. depolarization of presynaptic terminal causes opening of voltage-gated Ca+ channels
4. influx of Ca+ thru channels
5. Ca+ causes vesicles to fire with presynaptic membrane
6. transmitter is released into synaptic cleft via exocytosis
7. transmitter binds to receptor molecules in postsynaptic membrane
8. opening/closing of postsynaptic channels
9. postsynaptic current causes excitatory OR inhibitory postsynaptic potential that changes the excitability of the postsynaptic cell
10. removal of neurotransmitter by glial cell uptake or enzymatic degradation
11. retrieval of vesicular membrane from plasma membrane
What are some steps in neurotransmission that are targets for therapies?
-blocking the AP via Na+ channel inhibitors
- blocking the Ca+ influx via Ca+ channel blockers
- blocking vesicle release via botulinum/tetanus toxin
-inhibit or activate the receptor (curare)
-block inactivation/uptake of neurotransmitter (prozac)
What are these?
GABA and glycine
Biogenic amines – norepinephrine, epinephrine, dopamine, serotonin, histamine
small molecule neurotransmitters
What are these?
Brain – gut peptides (substance P, cholecystokinin octapeptide, vasoactive intestinal peptide)
Opioid peptides – enkephalin, endorphins, dynorphin
Pituitary peptides – vasopressin, oxytocin, ACTH
What are some unconventional neurotransmitters?
For small molecule neurotransmitters, where are enzymes synthesized? Where does synthesis and packaging of the neurotransmitter occur?
enzymes are synthesized in the cell body and then transported to the nerve terminal; synthesis and packaging of the neurotransmitter is done in the terminal
Where are neuropeptides synthesized for packaged? What happens to loaded vesicles?
neuropeptides are synthesized and packaged into vesicles in the cell body; loaded vesicles are transported to the nerve terminal for release
So how does packaging/transport differ in small body molecules vs neuropeptides?
in small body molecules, enzymes are synthesized in cell body but neurotransmitter is not synthesized/packaged until it reaches the nerve terminal; in neuropeptides, the neuropeptide is synthesized and packaged while in the cell body and then transported to the nerve terminal for release
For unconventional neurotransmitters, where are enzymes synthesized? Where is neurotransmitter synthesized?
Enzymes synthesized in the cell body and then transported to the nerve terminal; synthesis of neurotransmitter done in the terminal
**like small body molecules
Old school vs new school way of defining a neurotransmitter:
Old school – The substance must be present (blank) in vesicles.
New school – The substance can be synthesized (blank) (unconventional neurotransmitters).
presynaptically; on demand
Old school vs new school way of defining a neurotransmitter:
Old school – The release of the substance must be triggered by an increase in (blank) concentration.
New school – The substance can be synthesized (blank) by Ca2+-activated enzymes and diffuse out of the presynaptic cell (unconventional neurotransmitters).
presynaptic Ca2+; on demand
T/F: All release of neurotransmitter is Ca+ dependent.
Old school – Specific receptors for the substance must be present on the (blank) of the postsynaptic cell.
New school – Specific receptors for the substance can be present in the (blank) of the postsynaptic cell (unconventional neurotransmitters).
plasma membrane; cytoplasm
What is this?
Vesicles bud from the endosome and fill with transmitter
Vesicles dock at release site
Vesicles fuse into the plasma membrane
Vesicle membrane retrieved by clathrin-mediated endocytosis
Vesicles return to the endosome.
traditional model for vesicle recycling
What step in neurotransmitter release are SNARES involved in?
priming of vesicle to undergo exocytosis
What step in neurotransmitter release is synaptotagmin involved in?
coating of vesicle to be endocytosed
Some experiments find that vesicle fusion is not complete. These results are consistent with a partial emptying of the vesicle. What is this process referred to as?
Kiss and run **suggests that vesicles are competent enough to release a bit at a time allowing for rapid vesicle recycling as opposed to vesicle destruction
What happens to neurotransmitter release if extracellular Ca+ is removed or Ca+ entry is reduced or blocked?
release will be reduced or locked
T/F: Ca2+ entry is how a voltage-change across the membrane triggers this biochemical event. It is how a voltage-change triggers contraction of cardiac and smooth muscle. Contraction of skeletal muscle is different.
List two different Ca+ channels that are involved in neurotransmitter release. Where are these localized?
**localized to nerve terminals and dendrites, and neuroendocrine cells
Do neurons typically release one neurotransmitter, or several/many?
Neurons may release both a small molecule neurotransmitter and a neuropeptide. This is called co-transmission. What is required for the release of neuropeptide in many cases?
requires higher frequency of presynaptic AP and a greater elevation in intracellular Ca+
Where are the SNAREs located? Is SNAP-25 a SNARE?
one SNARE in a vesicle and one in the plasma membrane; SNAP-25 is not a SNARE but regulates the assembly of the other two SNAREs
How do SNAREs work?
When the vesicle docks, SNAREs pull the membrane of the vesicle toward the membrane of the neuron. Ca+ binds to SNARE, which catalyzes membrane fusion by binding to SNARE and plasma membrane.
Why is it important to consider the action of SNAREs?
This is a target for drug action.
Ion gradients contribute their (blank) to the membrane potential.
What is the Nerst equation?
Ex = RT/zF ln [X]o/[X]i
What's the membrane potential (Ex) of K+?
What's the membrane potential (Ex) of Na+?
+60 to +90mV
What's the membrane potential (Ex) of Cl-?
-88 to -35mV
What's the membrane potential (Ex) of Ca+?
The contribution of an ion gradient to the membrane potential is weighted by the (blank) of the cell membrane to that ion
a measure of how easy it is for a molecule or ion to cross a membrane
If the permeability of K+ is large, what happens to Em? If the permeability of Na+ is large, what happens to Em?
Em will be close to E(K); Em will be close to E(Na)
How is permeability set?
by the opening and closing of ion channels
**ex: ACh binds, and ion channel opens
What is another name for ligand-gated ion channels?
What is another name for G-protein coupled receptors?
If channels highly selective for Na+ open, (blank) increases, and membrane potential moves toward (blank).
PNa; ENa **NOT necessarily TO ENa, but close!! The larger the PNa, the closer to ENa
If channels highly selective for K+ open, (blank) increases, and membrane potential moves toward (blank).
Suppose channels open that allow both Na+ and K+ through the membrane. These are commonly called (blank).
Both PNa and PK will increase. What will happen to the membrane potential??
nonselective channels; the membrane potential will move toward a potential in between ENa and EK. Toward zero!!
Electrophysiologists call the potential that channels are moving the potential toward the (blank) or Erev
The reversal potential is the (blank) potential associated with the opening of a particular channel.
Opening a channel will shift the membrane potential towards (blank).
The more channels you open the closer the membrane potential will move to (blank)
Suppose the membrane potential is -65 mV (i.e. a normal RP). What happens if one opens nonselective channels?
the membrane potential will become LESS negative
Suppose a physiologist has hooked the cell to a device that shifts the membrane potential to +65 mV*. What happens if one opens nonselective channels?
the membrane potential will become MORE negative
Suppose a physiologist has hooked the cell to a device that shifts the membrane potential to 0 mV. What happens if one opens nonselective channels?
The membrane potential will move toward 0 mV, i.e. it will not change. This is the “reversal potential” or Erev.
T/F: The reversal potential is the target potential associated with the opening of a particular channel.
For a highly selective channel Erev is the Nernst equilibrium potential of the chosen ion.
For a poorly or non-selective channel Erev will be between the Nernst equilibrium potentials of the ions that pass through the channel.
What is the general rule for Erev?
The general rule…is that the action of a neurotransmitter drives the postsynaptic potential toward Erev (the target potential) for the particular ion channels being activated.”
**The value of Erev is determined by the relative permeability of the channels to Na+, K+, Ca2+, Cl
The main channels activated by neurotransmitters to generate receptor potentials are (blank) for monovalent cations or (blank) for Cl- or for Ca+. Channels activated by neurotransmitters that are highly selective for K+ and Na+ are (blank).
nonselective; selective; rare
If Erev (target potential) is positive to threshold the event is a (blank) making the postsynaptic neuron (blank) likely to fire an action potential.
excitatory postsynaptic potential (EPSP); more
If Erev (target potential) is negative to threshold the event is a (blank) making the postsynaptic neuron (blank) likely to fire an action potential.
inhibitory postsynaptic potential (IPSP); less
T/F: If Erev (target potential) is negative to threshold the event is an inhibitory postsynaptic potential (IPSP) making the postsynaptic neuron less likely to fire an action potential. **Even if Erev is positive to the resting potential!
Opening channels to allow for an inhibitory potential (usu Cl- channels) stabilizes the membrane potential near (blank) making it harder to get to threshold.
Erev (negative to threshold)
Ion channels nonselective for cations or selective for Ca2+ mediate (blank) (Erev positive to threshold)
Ion channels selective for K+ mediate (blank) (Erev negative to threshold)
Ion channels selective for Cl- mediate (blank) if ECl is negative to threshold or (blank) if ECl is positive to threshold.
If two action potentials arrive at the same time, what does this lead to? Is timing important?
summation **generates larger AP
Yes, timing is important - APs must arrive at about the same time
EPSPs and IPSPs are additive, but are they always linear?
No; may cause a decrease in the AP when they sum
T/F: The summation of EPSPs and IPSPs is not linear
Postsynaptic neurons can signal back to the presynaptic neuron. What is this called? What are some examples of transmitters that can exhibit this behavior?
retrograde signaling; NO, CO, endocannabinoids, prostaglandins