GABA Transmitter System & Synaptic Inhibition Explained (Shunting Inhibition, GABAa, GABAb) | Clip

Welcome to Science With Tal!
In this video, we will cover the neurotransmitter: GABA. More precisely, we will cover its synthesis pathway, its ionotropic receptor (GABAa) & metabotropic receptor (GABAb). GABA is the principal inhibitory neurotransmitter in the CNS so it is important to understand its properties. Throughout this discussion, we will discuss how GABA inhibits cells including the process of shunting inhibition.
This conversation on neurons in the CNS derives from important concepts that are described in two previous full discussions:
1- To watch the first part (Signal propagation in the Neuron), make sure to go to: • Signal Propagation In ...
2- To watch the second (The Neuromuscular Junction as the model of the chemical synapse) make sure to go to: • Neuromuscular Junction...
To improve the quality of my content, I highly value the feedback from the viewer so do not hesitate to give any feedback in the comment section.
TIMESTAMPS
0:00 Introduction
0:15 Synthesis & reuptake
3:18 Ionotropic channel structure & mechanism (GABAa)
11:17 Metabotropic channel (GABAb)
12:50 3 forms of inhibition
13:33 Word on glycine
14:18 Conclusion
RESOURCES
Here is a list of the resources that I’ve used to produce this video. (Author(s): title resource)
- Dale Purves: Neuroscience (6th edition)
- Eric Kandel: Principles of neural science (6th edition)
- Lodish: Molecular Cell Biology (9th edition)
- Niswender, Colleen M, and P Jeffrey Conn: Metabotropic glutamate Receptors: physiology, pharmacology, and disease
- Bünemann, M et al: Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents
- Howlett, Allyn C et al: CB(1) cannabinoid receptors and their associated proteins
- Morris, R G: D.O. Hebb: The Organization of Behavior, Wiley: New York; 1949
- Stent, G S: A physiological mechanism fo Hebb’s postulate of learning
To have more information on these resources, you can refer to the conclusion section where a more formal citation is provided.
CREDITS
Writing: Tal Klimenko
Voice: Tal Klimenko
Animations: Tal Klimenko
Drawings: Tal Klimenko
Editing: Tal Klimenko
Introductory jingle: Thierry Du Sablond
Conclusion music: lukrembo - sunflower ( • lukrembo - sunflower (... )

[@Blush-wu8zj]

Hello, I got a question about the inhibition of VGCC channels by GABA B! If I understood it correctly, this inhibits the transmitter release in the presynapse (snare complex needs calcium on synaptotagmin for exocytosis). What is meant by the presynapse, is it the presynapse of the next synapse, between the axoterminal of the cell whose dendrites have GABAb receptors and the next neuron? Or is it the presynapse of the same synapse, where GABA B was originally released? The latter doesnt seem to make sense because if GABA B is released less due to VGCC block, the postsynaptic cell would generate less IPSPs being rather excitatory? Thank you in advance!!

[@sciencewithtal]

Hi, good question! It is the presynaptic terminal of the neuron that releases GABA. So basically this GABA B mechanism is autocrine (signals on the same cell). At 13:27 on panel 3 I show what it should look like. From my understanding, this mechanism is useful for the presynaptic cell to prevent releasing too much GABA and leading to over-inhibition.

[@Blush-wu8zj]

​@@sciencewithtal Thank you for your swift answer! 😊❤

[@violettebri]

Hello, great video! One question: the "Synthesis & reuptake" part - can you tell me the exact sources that you used for that part. I'm well aware you've got all your sources in the description, but I'd like to read the exact source. Thank you

[@sciencewithtal]

Hi, I used the textbook Principles of Neural Science (6th version) to cover this section. The passage that discusses this topic of the video is in chapter 16 (neurotransmitters) and there is a figure (Fig 16-1) that illustrates the reuptake process. If you do not have the textbook, send me an email at [e-mail] and I'll send you the figure. Hope this helps!

[@violettebri]

Thank you so much! I appreciate you replying to quick as you did. I'm currently writing an exam and this was so helpful. @@sciencewithtal

[@sciencewithtal]

@@violettebri My pleasure, good luck!

[@violettebri]

​@@sciencewithtal I finished my exam with an A !!, and I wanted to say thank you so much! I've been watching your videos throughout this exam period, and they truly helped me gain a visual understanding of the material. Have a great summer!

[@sciencewithtal]

@@violettebri Glad I could help, good job!!!

[@Pumiki]

12:03 The receptor is GABA-B and the subunits alpha-beta-gama combined are the Gi protein, right? So why does the receptor named "Gi"?

[@sciencewithtal]

Good question, its just a matter of notation for me. I like to indicate on the receptor what G protein it recruits but obviously the receptor is not part of the G protein.

[@lukasin6242]

When GABA is released, it connects to both GABA A and GABA B recpetors?

[@sciencewithtal]

Yes, GABA is an agonist/ligand for both receptors. It will bind to both if GABA A and GABA B receptors are both present on the postsynaptic neuron. Let me know if there is anything else!

[@Nawwar.]

So with GIRK channels, they always lead to a pottasium efflux hence hyperpolarization? If so where does the name 'inward rectifier' comes from?

[@sciencewithtal]

Hi, very good question! Sorry for the delay I had never seen your comment until now. Anyhow, here is my interpretation and to understand where I am coming from I suggest taking a look on Google at images of "inward rectifying iv curves": So, if you consider an IV curve with the voltage on the x-axis and the current on the y-axis, with positive values of y being an outward current (hyperpolarization) and negative values of y being an inward current (depolarization) you will notice that inward rectifiers produce an inward current only when the membrane potential is lower than the reversal potential of potassium (Ek) and when the membrane potential is above the channels produce an outward current. As you can see in the different pictures, the outward current that they produce is variable depending on the channel subtype. In my understanding, their use is sort of similar across the board. If we consider a neuron with a membrane potential (Vm) at -70 mV. When these channels open due to the mechanism explained in the video, they will lead to an outward current because Vm is greater than Ek. However, if the neuron gets hyperpolarized to lets say -85 mV and we assume for simplicity that Ek is -80 mV, then the channels will produce an inward current to buffer the hyperpolarization. So basically, these channels do produce both inward and outward currents but I think the name of inward rectifiers may have came because when you look at their IV curves, it is only the inward portion that is linear, which means that the channels can buffer the hyperpolarization at any membrane potentials but the same cannot be said about the outward current for most inward rectifier channels. I hope this makes sense and do not hesitate to correct me on anything!

[@learnwithme2315]

Is the chlorides equilibrium potential not around -60mV?

[@sciencewithtal]

Yes, it can be. The equilibrium potential for chloride can vary quite a bit depending on its intracellular concentration. The value that is chosen in the video is 4 mM but in mammalian neurons it can vary between 4 and 30 mM.