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2021-11-03 11:57:39 -07:00
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18
neurotransmitters1.md
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@@ -62,7 +62,7 @@ The ionotropic receptors are the ones you’ve probably seen in our synaptic dia
Note:
retinal vision reference for metabotropic modulation of ion channel function
The photoelectric response (from bacteria to human retinal photoreceptors) depends on metabotropic modulation of ion channel function. Also the response to odorants in nasal epithelium for olfaction as well as certain chemosensory receptors for taste. And the receptors for neuropeptides, as well as biogenic amines like dopamine, norepinephrine, histamine, and serotonin
Metabotropic transmitter receptors are G-protein coupled receptors, also known as seven-transmembrane domain receptors in your cell biology courses.
@@ -74,16 +74,16 @@ Metabotropic transmitter receptors are G-protein coupled receptors, also known a
Effector enzymes for activated G-proteins include:
* Gs: --> adenylyl cyclase --> ATP--> cAMP --> PKA --> incr prot phosphor
* Gq: phopholipase C --> [DAG --> PKC; IP3 --> Ca^2+^] --> incr prot phosphor, Ca binding proteins
* Gi: --< adenylyl cyclase --< cAMP --< PKA --> decr prot phosphor
* Gs: --> adenylyl cyclase --> ATP--> cAMP --> PKA => incr prot phosphor
* Gq: phopholipase C --> [DAG --> PKC; IP3 --> Ca^2+^] => incr prot phosphor, Ca binding proteins
* Gi: --< adenylyl cyclase --< cAMP --< PKA => decr prot phosphor
* Or guanylyl cyclase (GTP->cGMP) --> Protein kinase G etc.
* All G-protein receptor activations lead to downstream second messsaging (cAMP, diacylglycerol, IP3) --> protein kinases, Ca2+ --> leading to phosphorylation state changes including... ion channels
* Three amplification steps here! (receptor production of G proteins, adenylyl cyclase production of cAMP, protein kinase substrate phosphorylation). Source signal amplification.
* 3% of our genome is codes for protein phosphorylation state genes (500 protein kinases and 200 protein phosphatases)
* cAMP dependent protein kinases (PKA)
* Ca^2+^ - calmodulin depedent protein kinase type II (CaMKII predominant in neurons, most abundant protein component of the post synaptic density)
* Ca^2+^ - calmodulin dependent protein kinase type II (CaMKII predominant in neurons, most abundant protein component of the post synaptic density)
* Protein kinase C (PKC)- activated by Ca^2+ (moves PKC from cytosol to membrane) and diacylglycerol (DAG) and then phosphorylates substrates
@@ -169,9 +169,9 @@ Most effects of nicotine go through nAChR
* Multiple isoforms for each subunit, depending on which isoform is in channel get different properties
* In neurons its slightly different. 5 subunits 3α:2β. Bungarotoxin only inhibits muscle nACh receptors
<figure><img src="figs/Neuroscience5e-Fig-06.03-1R_copy_312f80c.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 6.3</figcaption></figure>
<div><img src="figs/Neuroscience5e-Fig-06.03-1R_copy_312f80c.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 6.3</figcaption></div>
<figure><img src="figs/PN07100_copy_ba52d13.jpg" height="200px"><figcaption>Neuroscience 2e 2001</figcaption></figure>
<div><img src="figs/PN07100_copy_ba52d13.jpg" height="150px"><figcaption>Neuroscience 2e 2001</figcaption></div>
Note:
@@ -215,13 +215,13 @@ If this piece of membrane and channel is from a muscle cell than a bunch of thes
## Activation of nAChR at neuromuscular synapses
<div><figcaption class="big" style="width:500px">end plate currents in a voltage-clamped muscle cell</figcaption><img src="figs/Neuroscience5e-Fig-05.17-2R_copy_fe44356.jpg" width="400px"><figcaption>Neuroscience 5e Fig. 5.17</figcaption></div>
<div><figcaption class="big" style="width:500px">end plate currents in a voltage-clamped muscle cell</figcaption><img src="figs/Neuroscience5e-Fig-05.17-2R_copy_fe44356.jpg" width="350px"><figcaption>Neuroscience 5e Fig. 5.17</figcaption></div>
<div>
<figcaption class="big">
depolarizing end plate potential recorded
in muscle cell due to the inward end plate currents
</figcaption><img src="figs/Neuroscience5e-Fig-05.17-1_copy_fd2d12e.jpg" width="400px"><figcaption>Neuroscience 5e Fig. 5.17</figcaption></div>
</figcaption><img src="figs/Neuroscience5e-Fig-05.17-1_copy_fd2d12e.jpg" width="350px"><figcaption>Neuroscience 5e Fig. 5.17</figcaption></div>
Note:

16
neurotransmitters3.md
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@@ -42,12 +42,12 @@ This Ca^2+^ permeability depends on subunit composition of the nAchR pentamer. m
from [#Picciotto:2000]:
from [^Picciotto:2000]:
>some subtypes of nAChR in the brain (those containing the b2 subunit) are located diffusely throughout the membrane of the neuron, with no obvious concentration at the synaptic junction (Hill et al. 1993).
https://us02web.zoom.us/j/86077044985?pwd=USt1SGJ6Wm1VSitncWlmTjgzSmZrQT09
a number of alpha and beta subunits have expression throughout brain (medulla, superior colliculus, cortex, beta2 subunit expression 'very high' in thalamus). Only alpha3 KO mice have high mortality [#Picciotto:2000].
[#Picciotto:2000]: Picciotto, M. R., Caldarone, B. J., King, S. L., and Zachariou, V. (2000). Nicotinic receptors in the brain. Links between molecular biology and behavior, Neuropsychopharmacology, 22(5), 451-65. PMID 10731620
[^Picciotto:2000]: Picciotto, M. R., Caldarone, B. J., King, S. L., and Zachariou, V. (2000). Nicotinic receptors in the brain. Links between molecular biology and behavior, Neuropsychopharmacology, 22(5), 451-65. PMID 10731620
Low (nM) concentrations of nicotine are found in the blood of moderate smokers (Henningfield et al. 1983). These are sufficient to enhance excitatory transmission in cultures of neurons from the medial habenula or the hippocampus (Gray et al. 1996; McGehee et al. 1995) [#Picciotto:2000]
@@ -117,7 +117,9 @@ Ligand gated channels in general are made up of 4 or 5 subunit monomers.
* 5 or so isoforms
* mAChR blockers are used for pupil dilation (atropine), motion sickness (scopolamine) and asthma treatment (ipratropium)
<div><img src="figs/2006-10-25_Amanita_muscaria_crop_copy_6b3de79.jpg" height="200px"><figcaption>[*Amanita muscaria*, Onderwijsgek, CC BY-SA 3.0 nl](https://commons.wikimedia.org/w/index.php?curid=21983879)</figcaption></div>
<div><img src="figs/2006-10-25_Amanita_muscaria_crop_copy_6b3de79.jpg" height="200px"><figcaption>
[*Amanita muscaria*, Onderwijsgek, CC BY-SA 3.0 nl](https://commons.wikimedia.org/w/index.php?curid=21983879)</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-06.04-1R_copy_e029b6f.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 6.4</figcaption></div>
@@ -204,10 +206,10 @@ GluR1 | GluR5 | NR1 | mGluR1
GluR2 | GluR6 | NR2A | mGluR5
GluR3 | GluR7 | NR2B | mGluR2
GluR4 | KA1 | NR2C | mGluR3
| KA2 | NR2D | mGluR4
| | NR2D | mGluR6
| | NR3A | mGluR7
| | NR3B | mGluR8
GluR5 | KA2 | NR2D | mGluR4
| | NR2D | mGluR6
| | NR3A | mGluR7
| | NR3B | mGluR8
</div>

7
pain.md
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@@ -89,6 +89,13 @@ receptors for transduction of mechanical and chemical forms of nociceptive stimu
NAV 1.7 and NAV 1.8 are sodium channels especially important for transmission of nociceptive information
2021 Nobel Prize David Julius (UCSF, TRP channels) and Ardem Patapoutian (Scripps, piezo receptors)
<https://www.universityofcalifornia.edu/news/david-julius-wins-nobel-prize-work-pain-sensation>
<https://www.nobelprize.org/prizes/medicines>
> “for their discoveries of receptors for temperature and touch”
<!-- ## Nociceptors