Communication Between Cells

Question 1

Synapses

Answer 1

-specialized junctions where communication b/w cells occurs

Question 2

2 main types of synapse

Answer 2

1) Electrical

2) Chemical

Question 3

Electrical Synapse

Answer 3

• direct electrical continuity b/w the pre- and postsynaptic cell
• a gap junction (channel) forms a low resistance pore b/w the cells
• molecules known as connexins form a hemichannel in each cell, known as a connexon, connexons from the 2 cells make a gap junction
• rapid, bidirectional, requires matching b/w the size of pre- and postsynaptic cells

Question 4

Chemical Synapse

Answer 4

• invasion of an AP leads to release of chemical transmitter which diffuses across a synaptic cleft to interact with ligand-gated channels in the postsynaptic membrane
• an electrical signal is transduced into a chemical signal
• unidirectional, synaptic delay, can change the sign of a signal or amplify a signal

Question 5

Gap Junction

Answer 5

• low resistance pore b/w cells during electrical synapse
• connexins form a hemichannel in each cell, known as a connexon (6 connexins form the connexon)
• the connexons from the 2 cells join to make a gap junction

Question 6

Steps in Presynaptic Chemical Neurotransmission

Answer 6

1. Transmitter is synthesized & stored in vesicles in the synaptic terminal
2. an AP invades the terminal
3. this depolarizes the terminal
4. depolarization serves to open voltage gated calcium channels leading to influx of Ca2+
5. Ca2+ causes fusion of synaptic vesicles with presynaptic membrane (via interaction with molecules known as SNARES). Release occurs in packets of a minimal size known as quanta (1 vesicle ~ 1 quanta)
6. transmitter is released into the synaptic cleft & diffuses across

Question 7

Steps in Postsynaptic Chemical Neurotransmission

Answer 7

1. transmitter binds to receptors (often ligand-gated channels)
2. opening or closing of ion channels occurs
3. postsynaptic currents cause membrane potential change
   - neurotransmitter must then be either metabolized or taken up to end transmission
   - presynaptically, vesicles are recycled & re-filled with transmitter

Question 8

Chemical Synaptic Transmission at the NMJ

Answer 8

• specialized for a high safety factor to ensure that every time a motoneuron releases transmitter, every muscle fiber it innervates has an AP & contracts
• “end plate,” many release sites for transmitter, high #’s of receptors, & high quantal content (basically the # of vesicles available for release) & high probability of release for each quanta, as well as high #’s of postsynaptic receptors

Question 9

What is the neurotransmitter at the NMJ?

Answer 9

-Acetylcholine

Question 10

What are the receptors at the NMJ?

Answer 10

-Nicotinic receptors

Question 11

Central (CNS) Synapses vs. NMJ

Answer 11

• simpler (anatomically) , more diverse, different transmitters & receptors (excitatory, inhibitory, modulatory)
• lower quantal content, less secure
• size of post synaptic potentials are smaller (thus requiring summation of many PSPs to reach threshold for an AP)

Question 12

Types of Transmitters in the CNS

Answer 12

• peptides, aa, biogenic amines

- purines, neuropeptides, siogenic amines

Question 13

Fast Transmission

Answer 13

-mediated by ligands (transmitters) binding to a ligand-gated channel

Question 14

Ligand-gated Channels

Answer 14

• integrated receptor (the binding site for transmitter is part of the same molecule complex as the channel)
• binding of ligand causes conformational change in the channel, resulting in gating (activation)
• key is that receptor & channels are part of the same molecular complex

Question 15

Neuromodulatory Effects

Answer 15

• effects that are not depolarizaion or hyperpolarization, but biochemical changes in the cell which alter function and/or excitability
• effects are mediated by G-protein coupled receptors
• effects can also be through effects other than ion channels (enzyme)

Question 16

G-Protein Coupled Receptors

Answer 16

• have 7 transmembrane spanning regions & when they bind a ligand, a conformational change facilitates interaction with a G-protein
• activated G-protein either interacts directly with an ion channel or indirectly via second messengers
• any effects of ligand binding on membrane potential are indirect via a signaling pathway

Question 17

When Ca2+ enters the synaptic terminal it interacts with?

Answer 17

SNARES (Soluble NSF Attachement Protein Receptor)

Question 18

SNARES

Answer 18

Examples: Syntaxin, SNAP-25, Synaptobrevin

• proteins that facilitate docking of transmitter-filled vesicles at the membrane and prime the vesicles for release
• Ca2+ facilitates fusion of the vesicle to the presynaptic membrane & exocytosis of the transmitter contents

Question 19

Lambert Eaton Myasthenic Syndrome

Answer 19

-autoimmune disorder where small cell carcinomas in the lung release abs against presynaptic Ca channels (L-type)

Question 20

Myasthenia Gravis

Answer 20

-autoimmune disease that targets the nicotinic ACH receptor at the neuromuscular junction

Question 21

Why are SNARE proteins of clinical interest?

Answer 21

1) they can be damaged by clostridial bacterial toxins botulinum & tetanus
- tetanus toxin & botulinum B, D, F, & G cleave synaptobrevin
- Botulinum C cleaves syntaxin
- Botulinum A & E cleaves SNAP-25
- Tetanus toxin appears to selectively target inhibitory (GABAergic) synaptic transmission
- Botulinum toxin acts to prevent release of ACh at the NMJ

Question 22

Botox

Answer 22

-blocking ACh release at NMJ, resulting in paralysis

Question 23

Post Synaptic Potentials

Answer 23

-graded potentials

Question 24

Excitatory Post-synaptic Potential

Answer 24

• due to opening channels with permeability to cations, usually a mixture of Na+ and K+ (sometimes Ca2+)
• this drive membrane potential towards a weighted average of the equilibrium potentials (predicted by Nernst potential) for the ion species involved
• generally near 0mV and thus above threshold for AP (so inc. likelihood of an AP occuring)

Question 25

Excitatory Amino Acids

Answer 25

-Glutamate or Aspartate: most common mediators of fast EPSPs in the CNS

Question 26

Inhibition

Answer 26

-due to actual hyperpolarization or due to shunting of excitatory current so that threshold is not attained

Question 27

Most common inhibitory transmitter in the brain?

Answer 27

GABA - bind to ligand-gated receptors primarily permeable to anions (Cl-)

Question 28

Most common inhibitory transmitter in the spinal cord?

Answer 28

Glycine - bind to ligand-gated receptors primarily permeable to anions (Cl-)

Question 29

Temporal Summation

Answer 29

• occurs when two PSPs elicited in the same synapse occur close enough in time so that the first PSP has not completely decayed b/f the second occurs
• this time window is determined by the membrane time constant (a function of its RC properties)

Question 30

Spatial Summation

Answer 30

-refers to addition of effects of 2 different synapses that are close enough in location (must occur within a restricted time window)

Question 31

Brain Energy Metabolism Resting State

Answer 31

• glucose enters brain cells and is metabolized through the glycolytic pathway to form pyruvate & lactate
• Pyruvate: enters mito where it is metabolized via the citric acid cycle to generate ATP through oxidative phosphorylation, ATP generated equilibrates w/phosphocreatine to establish the cell’s energy storehouse
• even in resting states there is continued leakage of Na+ into neurons and K+ out, if leakage is unchecked it would eventually reach depolarization threshold & render neuron incapable of receiving a synaptic signal
• maintenance of Na+, K+, Ca2+ is accomplished via membrane pumps that are dependent on high energy phosphates (critical)
• in early infancy & under starvation, brain’s chemistry may shift to utilize ketone bodies

Question 32

Brain Energy Metabolism Activated State

Answer 32

• release of glutamate by the presynaptic bouton on the left triggers postsynaptic membrane depolarization & ion shift in the postsynaptic cell
• glutamate released into the synaptic cleft must be taken back into cells & this occurs in an adjacent astrocyte
• this reuptake of glutamate into astrocytes occurs via Na+ membrane transporters with a stoichiometry of 3 Na+ ions taken up for each glutamate molecule (inc. in intracellular Na+ activates the Na,K APTase pump to normalize intracellular Na
• inc. use of APT activates glycolysis with the production of lactate, the substrate for glycolysis is glucose delivered to thw astrocyte from circulation
• lactate produced in the astrocyte can be transported to the pre and postsynaptic neurons for further metabolism back to pyruvate with additional generation of APT