eSagan 🇮🇳 @crackurbones@qoto.org
Joined Nov 2019
🔴 Receptors
🔸 The next hurdle is to make sure that the postsynaptic cell receives that message. And it receives the message through a type of multi-protein complexes called receptors.
🔸 The trans-membrane protein-complexes in the cell membrane form a pore, and through this pore, the ions can travel. So, the Potassium ions can go out, the Sodium ions can come in, and Chloride ions can come in.
Normally these receptors are closed and the ions can't come in. But, when a neurotransmitter binds to the receptor, or a couple of neurotransmitter molecules bind to the receptor, the receptors open and the pore becomes available for the ions to travel along.
🔸 And which way they travel? Depends on the type of receptor. And so, as it turns out, we have two basic classes of receptors.
🔸 There are receptors that have an excitatory effect. Any receptor that takes the membrane potential closer to 0 (from -65mV) is an excitatory receptor.
🔸 On the other hand, if there is a receptor that actually takes the membrane potential away from zero, making it even more negative — thus taking it away from the threshold for the action potential — is an inhibitory receptor.
🔸 The most ubiquitous excitatory receptor is a a glutamate receptor. And the most ubiquitous inhibitory receptor is a GABA receptor.
🔸 The neurotransmitter involved that binds to the inhibitory GABA receptor is a GABA molecule. And the neurotransmitter that binds to the excitatory glutamate receptor is glutamate.
🔸 In Myasthenia Gravis, there are antibodies that the body makes by mistake against these acetylcholine receptors. And so, the antibodies destroy acetylcholine receptors. And therefore, the signal is sent from the motor neuron terminal, but it is not received by the muscle.
🔸 We know that the motor neuron terminal can release acetylcholine and we need to stop degradation of acetylcholine. We're going to give acetylcholinesterase inhibitor to try and keep the acetylcholine around longer, so that it can find it's way to the few remaining acetylcholine receptors.
🖼️ Image source: https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/neurotransmitters-their-receptors
Major #Greenland glacier collapse 90 years ago linked to #climatechange https://t.co/uLTMS6foPk
https://twitter.com/physorg_com/status/1237744019012300801?s=09
#Microbes could influence your desire to get outside
https://t.co/wnIZEYUCmW
https://twitter.com/medical_xpress/status/1237744128731090944?s=09
🌱 AMAZING Small Farm in France Under TREES! // Aromath Farm
https://www.youtube.com/watch?v=HAZwj23DxVE
We May Have Finally Found a Chunk of Theia Buried Deep Inside The Moon
https://www.sciencealert.com/we-may-have-finally-found-a-chunk-of-theia-buried-deep-inside-the-moon
The Fastest Supercomputer on Earth Is Being Deployed Against Coronavirus - ExtremeTech
https://www.extremetech.com/computing/307381-the-fastest-supercomputer-on-earth-is-being-deployed-against-coronavirus
The US Department of Energy has announced that the Summit supercomputer will be used to attempt to find a treatment or cure for Covid-19.
🔸 Between two neurons lie the pre-synaptic cell and the post-synaptic cell (cells with the synaptic terminal). They are separated by a short distance called the 'synaptic cleft'.
And the molecules of nerve transmitter are going to make their way from pre-synaptic cell to post-synaptic cell through the synaptic cleft.
🔸 Neurotransmitters need to have a termination, if they are not received by the post-synaptic cell. We use three different mechanisms to terminate the message of a neurotransmitter.
1️⃣ Diffusion: The molecules are simply going to diffuse out if they don't make it to the "ears" of post-synaptic terminal of the receiving neuron. So diffusion is a very effective way to terminate a message.
2️⃣ The second way is through something called re-uptake. And re-uptake is typically in the pre-synaptic terminal. There are channels, or transporters, which take neurotransmitters back up. The neurotransmitters get re-packaged and put back into a new vesicles (which are actually recycled as well).
🔸 And this is really important for drugs like #serotonin and #dopamine. And there are drugs that act on the serotonin and dopamine re-uptake transporters that can be used both therapeutically, for instance, to treat depression.
3️⃣ The third way that we terminate a message is through degradation. And in the case of degradation, what we have is enzymes that sit in the synaptic cleft that are just chewing up neurotransmitters. [GIF]
🔸 The molecule that the neurotransmitter where degradation is really important is #acetylcholine.
So, in case of acetylcholine, there is an enzyme that sits between the pre-synaptic and the post-synaptic cells, eating up acetylcholine, called acetylcholinesterase (AChE).
🔸 Acetylcholine is the neurotransmitter that is used by motor neurons. And so, in fact, blocking #acetylcholinesterase can be used for therapeutics — in the case of people that are not releasing enough acetylcholine, or don't have enough receptors for the acetylcholine.
🔸 We can boost the amount of acetylcholine in the cleft by inhibiting the acetylcholinesterase. And that's useful for people with diseases such as myasthenia gravis.
Clostridial Toxins: #Botox
🔸 Botox is one of several clostridial toxins made by clostridial bacteria. And the full name of Botox is actually botulinum toxin.
🔸 The vesicles are held very close to the cell membrane. What holds them? A group of three proteins, two of them anchored in the cell membrane, one of them anchored in the vesicle membrane. This complex is called the snare complex.
🔸 And what happens when calcium comes in is that it changes snare complex's shape. Ca²⁺ changes snare's configuration to being in a straight line. [see GIF]
🔸 So that pushes the vesicle into the plasma membrane and fusion Is inevitable. It takes a lot of energy for them not to fuse, and when they're that close, it's inevitable.
🔸 It's the snare pin's sensitivity to calcium that is the final event that allows the vesicle to fuse with the cell membrane.
🔸 Botox comes in and cuts a particular protein of these proteins of the snare pin. But the clostridial toxins cut a variety of places in these three proteins that make up the snare pin.
🔸 If the snare pin is broken for whatever reason, if that is cut, then release doesn't happen.
🔸 Nowadays, we use clostridial toxins all the time — and we use them for very serious problems, such as focal dystonia, where there is an inappropriate continual contraction of a muscle, and that is a basal ganglia disorder.
💉 So, the Botox is injected at a very low dose, very locally.
And Botox is used for a large variety of treatments of various disorders. It's also used cosmetically.
🔸 And the interesting thing about it's use in cosmetics is that, before the widespread use of Botox, we made our own wrinkles. And what Botox is doing is preventing the motor neuron from releasing the neurotransmitter on to the muscle, and thereby preventing us from actively making our own wrinkles.
Babies who persistently struggle with sleep in their first year are more likely to have childhood anxiety https://t.co/ViVdRLX0Fc
https://twitter.com/MailOnline/status/1237593795010543618?s=09
New Intelligence on How the Female Brain Works - WSJ
https://www.wsj.com/articles/what-makes-the-female-brain-different-11583528929
The brain regions affected by declines in #estrogen during #menopause include the hypothalamus, which regulates body temperature; the brain stem, which regulates sleep and stress; the hippocampus, or memory center; and the amygdala, which is the emotional center of the brain.
🔸 How do we get the neurotransmitter out of the vesicle and out of the cell and make it able to go and affect another cell?
🔸 There is a cell membrane, but the cell also has a lot of other membranes that are inside. Inside in these things called organelles.
🔸 The fusion between two different membranes happens constitutively. And the challenge for a neuron is to stop that.
We can't have these vesicles fusing with the plasma membrane, with the cell membrane all the time. That would not work.
🔸 What we want to do is we want to make the vesicle fuse to the membrane **only when the action potential arrives** .
🔸 So the key to neurotransmitter release is two things:
1. We're going to suppress constitutive or ongoing release.
2. We are going to link the release that we want in the synaptic terminal to the action potential.
🔸 There is a molecule that suppresses constitutive release within the synaptic terminal.
🔸 When the action potential comes in, the membrane potential increases and it opens a particular type of ion channel that lets in calcium ions.
🔸 These are positively charged ions with two positive charges. And, these calcium ions are going to flood in to the synaptic terminal, and that is going to trigger release.
🔸 The release that happens of vesicles that contain neurotransmitters is only when the calcium concentration increases.
🔸 All that happens when the calcium concentration increases is that the vesicular membrane and the the cell membrane fuse.
And the calcium concentration only increases when the action potential arrives.
🖼️ Image source: screen-grab from https://www.coursera.org/learn/neurobiology/lecture/o4ZMY/neurotransmitter-release
The WALKING WATER Mystery (in SPACE and SLOW MOTION!) - Smarter Every Day 160
https://www.youtube.com/watch?v=KJDEsAy9RyM
🌱 ECO HOME: No Power, Water & Sewer connection in this house.
https://www.youtube.com/watch?v=LB5gzj0bmq0
New model is very good at predicting the charging time of a supercapacitor while also incorporating physics on the micro and nano scales. https://t.co/N7xGGWI81a
https://twitter.com/PhysicsWorld/status/1237389694918250496?s=09
🧫 The synaptic terminal has these entities here, which are called synaptic vesicles, and they're small, little organelles.
🧫 They're little vesicles made of a membrane; just like the cell has a cell membrane, these vesicles have a vesicular membrane.
The neurotransmitters are within the vesicular membrane.
🧫 And, the neurotransmitter can be any number of a number of different molecules — #Glutamate, #GABA, #Serotonin, #Dopamine, #Acetylcholine, #Glycine, #Norepinephrine, #Epinephrine, #Histamine, #ATP.
🧫 The neurotransmitters are packaged in vesicles. The second thing that's important about this is that we can use the synthesis of a #neurotransmitter as a therapeutic tool.
🧫 So, for instance, Dopamine is missing in #ParkinsonsDisease.
It's not that dopamine isn't made per say, that's there's a problem with making it — it's that the cells that make it die.
🧫 There's something called 'Mass Effect', which means that you take the starting chemical (the substrate) and then through a series of enzymatic processes reaction, through a series of enzymatic reactions, we end up with a neurotransmitter.
🧫 In the case of Dopamine, what we do to treat in most people with Parkinson's is that we give them the substrate — and so that (drug) is what is commonly known as #Sinemet or #Parcopa.
🧫 So we flood the system with substrate, and the goal is to get a little bit of that neurotransmitter out of the system.
Image source: https://in.pinterest.com/pin/11962755239342046/?lp=true
Machine learning illuminates material's hidden order
https://phys.org/news/2020-03-machine-illuminates-material-hidden.html
Extreme temperature can do strange things to metals. In severe heat, iron ceases to be magnetic. In devastating cold, lead becomes a superconductor.
The case for an AI that puts nature and ethics first, not humans
https://thenextweb.com/neural/2020/03/07/the-case-for-an-ai-that-puts-nature-and-ethics-first-not-humans-syndication/
Without Facebook and Twitter, This is How Organisms Stayed Connected Billions of Years Ago
https://www.news18.com/news/buzz/without-facebook-and-twitter-this-is-how-organisms-stayed-connected-billions-of-years-ago-2530549.html
⚡ Neurons sit at a resting membrane potential of about -65 mV.
⚡ Small little potential differences — which are on the order of less than one millivolt up to, say, five millivolts — can travel along the neuron.
⚡ They might travel, but they're going to peter out pretty quickly. So, it's not going to work to simply rely on these small potential changes if we have to go long distances.
⚡ The longest neuron that we possess is a cell that has a cell body right at the base of the spine. And it sends one process all the way down to the toe, and it sends another process all the way up to the medulla.
⚡ Because neurons are so long, we use something called the Action Potential. And the Action Potential goes really far up and comes back down in height. So, it's about 100 mV.
⚡ So from the resting memory potential (-65mV) to the top of the Action Potential — which happens at around, say, 20mVs or so — we're talking about roughly 100 millivolts of difference. And that can get communicated all the way up. That's not going to get lost.
⚡ And what carries that Action Potential is: —
We looked at potassium being in very high concentration in a cell and much lower outside a cell. The reverse is true for sodium.
And so, the sodium comes flooding in, and because it's positively charged, that's what takes the cell up to this very high membrane potential.
⚡ Now the ability for a neuron to communicate using an Action Potential is a slow process unless we add one more thing, and that is an insulator —essentially a very nice insulator —called myelin.
Joined Nov 2019
