Communication Between Cells Flashcards
1
Q
Synapses
A
-specialized junctions where communication b/w cells occurs
2
Q
2 main types of synapse
A
1) Electrical
2) Chemical
3
Q
Electrical Synapse
A
- 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
4
Q
Chemical Synapse
A
- 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
5
Q
Gap Junction
A
- 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
6
Q
Steps in Presynaptic Chemical Neurotransmission
A
- Transmitter is synthesized & stored in vesicles in the synaptic terminal
- an AP invades the terminal
- this depolarizes the terminal
- depolarization serves to open voltage gated calcium channels leading to influx of Ca2+
- 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)
- transmitter is released into the synaptic cleft & diffuses across
7
Q
Steps in Postsynaptic Chemical Neurotransmission
A
- transmitter binds to receptors (often ligand-gated channels)
- opening or closing of ion channels occurs
- 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
8
Q
Chemical Synaptic Transmission at the NMJ
A
- 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
9
Q
What is the neurotransmitter at the NMJ?
A
-Acetylcholine
10
Q
What are the receptors at the NMJ?
A
-Nicotinic receptors
11
Q
Central (CNS) Synapses vs. NMJ
A
- 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)
12
Q
Types of Transmitters in the CNS
A
- peptides, aa, biogenic amines
- purines, neuropeptides, siogenic amines
13
Q
Fast Transmission
A
-mediated by ligands (transmitters) binding to a ligand-gated channel
14
Q
Ligand-gated Channels
A
- 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
15
Q
Neuromodulatory Effects
A
- 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)
16
Q
G-Protein Coupled Receptors
A
- 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
17
Q
When Ca2+ enters the synaptic terminal it interacts with?
A
SNARES (Soluble NSF Attachement Protein Receptor)
18
Q
SNARES
A
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
19
Q
Lambert Eaton Myasthenic Syndrome
A
-autoimmune disorder where small cell carcinomas in the lung release abs against presynaptic Ca channels (L-type)
20
Q
Myasthenia Gravis
A
-autoimmune disease that targets the nicotinic ACH receptor at the neuromuscular junction
21
Q
Why are SNARE proteins of clinical interest?
A
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
22
Q
Botox
A
-blocking ACh release at NMJ, resulting in paralysis
23
Q
Post Synaptic Potentials
A
-graded potentials
24
Q
Excitatory Post-synaptic Potential
A
- 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)
25
Excitatory Amino Acids
-Glutamate or Aspartate: most common mediators of fast EPSPs in the CNS
26
Inhibition
-due to actual hyperpolarization or due to shunting of excitatory current so that threshold is not attained
27
Most common inhibitory transmitter in the brain?
GABA - bind to ligand-gated receptors primarily permeable to anions (Cl-)
28
Most common inhibitory transmitter in the spinal cord?
Glycine - bind to ligand-gated receptors primarily permeable to anions (Cl-)
29
Temporal Summation
- 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)
30
Spatial Summation
-refers to addition of effects of 2 different synapses that are close enough in location (must occur within a restricted time window)
31
Brain Energy Metabolism Resting State
- 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
32
Brain Energy Metabolism Activated State
- 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
