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Flashcards in Synaptic transmission week 3 Deck (20):
1

What are electrical synapses and what protein mediates them? What tissue are they most commonly found in?

Electrical synapses are also known as gap junctions. They allow for cellular communication via direct flow of electrical current btwn coupled cells via connexons. Connexons also allow for nutrient, metabolite, and water exchange. Electrical synapses/gap junctions are most commonly found in muscle, and very common in cardiac muscle. Also in smooth muscle and secretory cells. Note that there is no synaptic delay in electrical synapses-allow for very rapid communication. 

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2

What are chemical synapses? Be sure to discuss both types.

The arrival of an AP at the presynaptic terminal initates release of transmitter in the presynaptic neuron which crosses the synaptic cleft to bind to receptors on the postsynaptic cell. Transmission at chemical synapses is uni-directional (whereas electrical can be bi-directional)

directly-coupled synapses/ligand-gated receptor channels: when transmitter binds to them, they open and allow for ion flux which usually changes membrane potential (are ionic channels). the change in membrane potential can either be depolarizing (excitatory), hyperpolarizing (inhibitory), or may not involve any change in postsynaptic membrane potential

indirectly-coupled synapses: transmitter binds to a receptor that is not an ionic channel. binding to receptor (GPCR) initates a series of steps that ultimately changes function of postynaptic cellular proteins which can be ionic channels, enzymes, or other proteins

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3

Discuss what happens at a synpase as it pertains to ion flux and NT release in the pre and postsynaptic membranes.

When an AP reaches the presynaptic nerve terminal, it causes the opening of voltage-gated Ca2+ channels (N-type Ca2+ channels which differ from L- and T-type). These channels are localized to the membrane of the presynaptic terminal and open rapidly in response to depolarization. Ca2+ enters the presynaptic neuron and causes synaptic vesicles to fuse with the membrane. Binding of NTs to receptors in postynaptic cell membrane usually directly or indirectly causes opening of ionic channels. Note that directly cpupled receptors are only open when NT is bound. 

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4

Discuss the location of NT receptors in neurons and skeletal muscle vs tissue innervated by the ANS.

in neurons and skeletal muscle, postsynaptic receptors are usually localized to region of synapse itself. Postsynaptic cells innervated by the ANS often have receotrs more or less uniformly distributed over the cell surface

5

At neuromuscular junction, the area of muscle that comes into close proximity with the motorneuron terminal is specialized and is called what?

end plate

6

True or false. Each motorneuron innervates anywhere form a few dozen to 2000 individual muscle fibers but each muscle cell only has a single synapse with a motorneuron.

True.

7

The NMJ is a special type of synapse. One of its unique features is that it is enormous-it can exceed 1000 square microns (as opposed to 1-2 square microns for synapses in CNS). What is the reason for this?

Because the NMJ is designed such that an AP is produced in skeletal muscle fiber whenever there is an AP in the motorneuron innervating the fiber. In normal cases, threshold is not even a factor bc muscle def contracts. This is good bc if you are running from a bear, for example, you def want your muscles to contract!

8

In presynaptic motor neurons at the NMJ, each ACh vesicle contains about 10k molecules of ACh. The release of a single ACh vesicle is called a ___ of ACh. Such individual vesicle fusions occur spontaneously at a rate of about 1/second and each produces a _____ _____ _____ of about 1mV or less. When an AP arrives at presynaptic motorneuron terminal it causes the simultaneous fusion of several hundred vesicles, and thus the release of several million molecules of ACh. The resulting muscle membrane potental is much larger than the (previous blank).

quantum

miniature endplate potential (MEPP)

9

What is the difference btwn nicotinic and muscarinic ACh receptors? What ions flow through nicotnic ACh receptors and what is the result?

nicotinic: nicotine is an agonist. are seen in skeletal muscle. muscarinic are common in autonomic and CNS. both work in different ways but both respond to binding of ACh. the nicotinic ACh receptor is a ligand-gated channels. When ACh is bound, it allows approximately equal Na+ and K+ flux. the result is Vm is driven btwn 0 and -10 mV (very roughly half btwn Ek and Ena). Result is membrane depolarization.

10

At the bottom of junctional folds in the NMJ is what enzyme? What is its function? Be sure to include discussion of desensitization.

acetylcholinesterase. breaks down ACh and helps terminate postsynaptic potential change (called end plate potential). note that if ACh remains bound to receptors for a long period of time, these channels will spontaneously close which is known as desensitization. acetylcholinesterase prevents desensitization from occurring.

11

What is the name of the membrane potential developed in the postynaptic muscle fiber? Contrast this with that in nerves.

The membrane potential developed in the postsynaptic muscle fiber is called the end-pate potenial (EPP). Is different from excitatory postsynaptic postenials in the CNS, called EPSPs. Each motor endplate may have as many as roughly a million ACh receptors compared to a few thousand channels/receptors of postsynaptic neurons in CNS. This allows for a very large depolarization of the motor end plate in comparision to neurons in the CNS. The EPP can reach a peak membrane potential around -30 to -20 mV (this is a change of +60 to +70 mV) which is far more than is needed to produce a postsynaptic AP. In neurons, individual EPSPs are about 1-2 mV (due to limited number of postsynaptic receptors and small number of vesicles-sometimes only one-that fuse with the presynaptic membrane for each presynaptic AP). The EPP has been designed by nature to always produce an AP. In the CNS, the summation of several EPSPs is necessary tp produce a postsynaptic AP (which can also be opposed by inhibitory synapses)

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12

How does an AP propagate in a muscle fiber after ACh has been released and the nAChR have allowed Na+ and K+ flux?

nAChR are only present at the NMJ junction. voltage gated Na+ channels are located in the membrane of all other parts of the muscle cell and occur in high densities in the membrane that immediately surrounds the endplate. There is also a smaller amount of Na+ channels in the membrane of T-tubules. As the membrane in and around the endplate depolarizes, voltage gated Na+ channels in the muscle cell membrane open and lead to an AP. If not present, the membrane potential produced at the end plate would decrement in size at increasing distance from the end plate. The AP spreads over the surface of the muscle as well as in T-tubules. Propagation in T-tubules is much slower due to their small diamert and lower density of Na+ channles but the distance to be traveled is much shorter (although the path can be tortuous). 

13

What is the NT released at most excitatory synapses? What receptors does this NT bind to and how do they work? What role are these receptors thought to play?

1. glutamate

2. There are 4 types of glutamate receptors, 3 of which are ligand-gated (directly coupled) and one of which is indirectly coupled. All of these channels are relatively non-selective cation channels which means they allow both Na+ and K+ to cross the membrane. 

The two gluamate receptors we are responsible for are NMDA and non-NMDA (note: NMDA is a non-physiological aa). Non-NMDA receptors only need to be bound to glutamate to allow for Na+ and K+ flux. NMDA receptors need both to bind to glutamate and  significant membrane depolarization before they open. Depolarization is needed to displace the Mg2+ ion that is normally "stuck" in the membrane. NMDA receptors not only allow Na+ and K+ flux, but Ca2+ as well which can act as a second messenger to activate intracellular cascades

3. Maintained synaptic activity at these types of synapses is thought to be involved in some forms of information stroage in the brain and may be involved in pathological conditions such as epilepsy and stroke

14

What NT(s) are used in the CNS at inhibitory synapses? What are their receptors? What is the effect?

Note: in general, inhibitory synaptic transmission causes the postsynaptic cell to become less likely to fire an AP. The CNS contains both directly and indirectly coupled synapses but we will focus on directly coupled. 

Most directly coupled inhibitory synapses in the CNS use glycine or GABA (gamma-aminobutyric acid) as their NT. Note that while all glycine receptors are directly coupled, one type of receptor for GABA is a GPCR. glycine and GABA receptors are Cl- channels. Since Cl- permeable but is not actively transported, its Vm is very near or identical to resting Vm. So, the opening of these channels may have little or not effect on the transmembrane potential of the postysynaptic cell BUT when these channels open they attempt to hold membrane potential near ECl and therefore near resting Vm. They reduce changes in membrane potential that occur in reponse to opening of Na+ channel or excitatory postsynaptic channels making it more difficult to fire an AP. Inhibitory synapses may not produce any change in the postsynpatic membrane potential but when they do, they are called inhibitory postsynaptic potenials (IPSPs). For example, if the postysnaptic membrane is depolarized from resting due to excitatory synaptic transmission, Vm will be positive to ECl and opening of Cl- channels will draw Vm closer to ECl (i.e. toward resting). Note that there have been reports of inhibitory synapses that are permeable to K+.

15

Define spatial and temporal summation.

spatial: occurs when 2 or more (usually many more) separate presynaptic inputs arrive more or less simultaneously at different locations on the postsynpatic cell. synpatic potentials spread decrementally from their point of origin but they do spread and this allows spatial summation. It is the balance btwn excitatory and inhibitory synaptic influences that determines postsynpatic membrane potential. Note that presynaptic neurons closest to the axon hillock will have more effect on Vm

temporal: when two or more APs in a particular presynaptic neuron are fired in rapid succession such that the postsynaptic response to the first AP is not complete when the second AP arrives. results in larger postsynaptic response thatn would be produced by either presynaptic AP alone if more widely separated in time. 

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16

What type of channels are found in high numbers in the axon hillock that are thought to be scarce in the dendrites and soma?

voltage-gated Na+ channels. makes sense because is site of AP propagation.

17

Discuss presynaptic inhibition and facilitation and what effects they have. 

both presynaptic inhibition and facilitation occur through axo-axonic connections. they are not completely understood and their presence is still being debated.

presynaptic inhibition: an axon synapses on a presynaptic axon such that it causes less NT release from the presynaptic neuron. This causes less NT to be bound to the postsynaptic neuron. It is thought that this decrease in NT release from the presynaptic neuron is done by decreasing Ca2+ influx into the presynaptic terminal.

presynaptic facilitation: is the same as inhibition except for there is an increased amount of NT release from the presynaptic neuron thought to be due to an increase in Ca2+ ion flux at the presynaptic terminal.

The effects of presynaptic inhibition and facilitation are elongation or shortening of the presynaptic AP which results raising or lowering of postsynaptic Vm

Note that they do not directly produce postsynaptic effects but modulate the effectiveness of presynaptic inputs on postsynaptic cells.

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18

True or false: GPCR are not only in target organs of ANS but are very common in CNS. Some GPCRs are receptors for epinephrine, norepinephrine, ACh, glutamate, dopamine, serotonin, GABA, and neuropeptides. The often involve second messenger systems (like cAMP, PKA), effects are less localized than directly coupled synapses, and effects are longer lasting than directly coupled synapses. 

True. see pg 185 of course notes for longer explanation.

19

  What are neuropeptides/neuromodulators? How are they released, from where are they released, and what are their effects? What types of receptors do they bind to?

neuropeptides/neuromoldulators are relatively large molecules that are stored in dense-core vesicles that are often also present in nerve terminals. Dense core vesicles fusing with the membrane is Ca2+ dependent just like for synaptic vesicles, but their release generally requires a high frequency of APs at the presynaptic nerve terminal. Neuropeptides always bind to GPCR that may be in the presynaptic membrane, postsynapctic membrane, or both. Neuropeptides are often called neuromodulators bc they bring about long term changes that can enhance or depress synaptic effectiveness or other cellular functions. Some modes of action include changes in NT synthesis and changes in the number of postsynaptic channels. See pg 186 of course notes for visual.

20

True or false: Both directly-coupled and indirectly-coupled receptors are found in the CNS while only indirectly-coupled receptors occur in the membranes of target organs innervated by the ANS.

True.