jackman/biol125-lectures
1
0
Fork 0
Code Issues Pull Requests Releases Wiki Activity

lect fin fall 2020

Browse Source
This commit is contained in:
ackman678
2020-12-14 10:18:11 -05:00
parent 93d862046c
commit 9a9e0c7b14
13 changed files with 397 additions and 167 deletions
Download Patch File Download Diff File Expand all files Collapse all files

56
neurotransmitters3.md
View File

@@ -1,11 +1,31 @@
## Cholinergic receptors
* Best studied– the nicotinic ACh receptor (nAChR)
## Neurotransmitter receptors
<div style="font-size:0.8em">
<div></div>
* Neurotransmitter receptors
1. **ionotropic**, a 'ligand-gated' ion channels
2. **metabotropic**, a G-protein coupled receptors that modulate separate ion channels
* Neurotransmitter receptor activation following ligand (neurotransmitter) binding results in the opening of ion channels and ionic flux. This ion flux is the postsynaptic current (or 'end plate' current for a muscle cell)
* These postsynaptic currents result in depolarization or hyperpolarization of the membrane potential (postsynaptic potential or 'end plate' potential) depending on the **types of ions** flowing through the channel pores and the ions' respective **electro-chemical driving forces**
</div>
<div style="font-size:0.5em;">
<!-- date: -->
</div>
---
## nAChR
* Pentamer- 5 subunits to make a pore. Selective for cations
* Nicotine can mimic ACh to stimulate receptor, this is called an agonist. Most effects of nicotine go through this receptor
* nACh receptors produce EPSPs
* Many toxins specifically bind to and block nicotinic receptors called antagonists
* alpha-bungarotoxin (snake venom)– binds to alpha subunit of nAChR very tightly and prevents ACh from activating it
- Pore diameter 10x greater than voltage-gated Na⁺ channels (3 nm vs 0.3 nm)
* Nicotine mimics ACh to stimulate receptor, an agonist
* nicotinic ACh receptors (nAChR) produce excitatory postsynaptic potentials (EPSPs or EPPs)
* Many toxins specifically bind and block nAChR; these are antagonists
* alpha-bungarotoxin (snake venom)– binds to alpha subunit of nAChR very tightly and prevents ACh from activating it
Note:
@@ -24,7 +44,7 @@ This Ca^2+^ permeability depends on subunit composition of the nAchR pentamer. m
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
@@ -34,39 +54,37 @@ Low (nM) concentrations of nicotine are found in the blood of moderate smokers (
Many effects of nicotine probably through presynaptic or preterminal nAChRs instead of through postsynaptic AChRs (Léna et al. 1993; Marshall et al. 1997; McGe- hee et al. 1995; Summers and Giacobini 1995; Vidal and Changeux 1993; Wonnacott et al. 1990; Yang et al. 1996) [#Picciotto:2000]
Most effects of nicotine go through nAChR
<!-- nAChR
* Green is motor axons, red is where Bungarotoxin binds, defines the endplates
<div><img src="figs/image2_a9b00a8.png" height="100px"><figcaption></figcaption></div> -->
---
--
## Structure of the nACh receptor
* 5 subunits come together to make a pore
* Each subunit has 3-4 membrane spanning domains
* In muscles the receptor has 2α, β, δ, γ, ε subunits. The α subunits bind ACh, both need to be bound for channel to open. α subunits also binds bungarotoxin and nicotine
* 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 style="width:200px; float:left;"><img src="figs/Neuroscience5e-Fig-06.03-1R_copy_312f80c.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 6.3</figcaption></div>
<div><img src="figs/PN07100_copy_ba52d13.jpg" height="200px"><figcaption>Neuroscience 2e 2001</figcaption></div>
Note:
The alpha subunits bind ACh.
---
## Muscle nAChR
Muscle nAChR
* Pentamers of 2α1, β1, γ, δ in fetal mammals vs. 2α1, β1, δ, ε in adult mammal
* ACh, nicotine, curare, and bungarotoxin binding sites are on the α1 subunits
* Pore diameter 10x bigger than Na⁺ channels (3 nm vs 0.3 nm)
* Multiple isoforms for each subunit, depending on which isoform is in channel get different properties
<figure><img src="figs/PN07100_copy_ba52d13.jpg" height="200px"><figcaption>Neuroscience 2e 2001</figcaption></figure>
In neurons its slightly different. 5 subunits 3α:2β. Bungarotoxin only inhibits muscle nACh receptors
Note:
Changes in subunit composition during development.
curare is a competitive antagonist.