neurotransmitters

[Math Is Hard]

When neurotransmitters are released into the synaptic gap, do they bind with receptors only once and then disengage once, or do they bind and disengage repeatedly?

Thanks.

[neurocomp2003]

its once isn't it...cuz of the all or none firing principle...that once teh NT are received by the receptors of the post synapse that they enter the knob for decomposition?

[Moonbear]

It depends on the neurotransmitter. Some, when bound to their receptor, are internalized into the cell along with the receptor and once perform their signalling function, are degraded within the cell. Others stay at the membrane where they can continue interacting until endocytosed by the cell releasing them. This would also depend on whether the action was postsynaptic or presynaptic as to how much recycling could occur.

Neurocomp, all-or-none firing does not refer to NTs binding once, but to the propagation of an action potential once a threshold potential is reached.

[quasi426]

Others stay at the membrane where they can continue interacting until endocytosed by the cell releasing them. This would also depend on whether the action was postsynaptic or presynaptic as to how much recycling could occur.


I'm a little bit confused here. Isn't endocytosed and internalized the same thing. How can the cell release something during endocytosis.

[gerben]

The unbound neurotransmitter in the synaptic cleft will be disposed of by diffusion, enzymatic degradation and/or reuptake. If this happens quickly the neurotransmitter will probably bind only once (e.g. acetylcholine at neuromuscular junction). If is does not happen very quick they can bind more than once and have a prolonged effect, neuroactive petides are removed slower than small-molecule transmitters and so their effects are of longer duration.

its once isn't it...cuz of the all or none firing principle...that once teh NT are received by the receptors of the post synapse that they enter the knob for decomposition?

The “all or none firing principle” has nothing to do with this. If the membrane potential of the cell body of the postsynaptic neuron changes then an action potential will be send out trough its axons only when the membrane potential at the start of an axon (the axon hillock) reaches a certain threshold. It does give an action potential or it does not, so it is “all or none”.

[Math Is Hard]

Thanks! :smile: You know, I didn't realize that the NT would remain attached to the receptor in some cases. I thought the fate of the NT was always reuptake by the presynaptic neuron or destruction by the MAO process.

When you say that some stay at the membrane where they can continue interacting, does that mean they release and re-bind with other receptors, or the same receptor, or maybe both? I guess I imagine some of these little NTs bouncing from receptor to receptor, propigating a new action potential with each binding, but I am not sure if it can work that way.

edit: sorry, Gerben, I replied before I saw your post. I was responding to Moonbear's post.

[gerben]

When you say that some stay at the membrane where they can continue interacting, does that mean they release and re-bind with other receptors, or the same receptor, or maybe both?

Yes, I believe both can happen.

I guess I imagine some of these little NTs bouncing from receptor to receptor, propigating a new action potential with each binding, but I am not sure if it can work that way.

They would not "propagate an action potential" with each binding, but modulate the membrane potential with each binding. Whether an action potential results depends on the membrane potential at the start of the axon (the so-called axon hillock).

[Math Is Hard]

Thanks, gerben. I think I am beginning to understand a little better now. I am going to do some more reading tonight. I've got this book on physiology of behavior that I have been reading just to try to get a deeper understanding of some of the things covered in my psychology and biology classes.

[Moonbear]

I'm a little bit confused here. Isn't endocytosed and internalized the same thing. How can the cell release something during endocytosis.

Sorry, my distinction wasn't between endocytosed and internalized but between the presynaptic or postsynaptic cell. I didn't word that very well. Others have explained better anyway.

MIH, what book are you reading?

[DocToxyn]

I thought the fate of the NT was always reuptake by the presynaptic neuron or destruction by the MAO process.


Just to clarify, the enzymatic destruction of a neurotransmitter at the synaptic cleft is mediated by many different enzymes, monoamine oxidase (MAO) being only one of them. MAO is typically implicated in the metabolism of catecholamines like dopamine or norepinephrine, although DA in the cleft is first hit by catechol-o-methyltransferanse (COMT) to form 3-methoxytyramine, which is then very rapidly metabolized by MAO to homovanillic acid (HVA). On the intracellular side, DA is metabolized by MAO (The b form) to dihydroxyphenylacetic acid (DOPAC). However, I think the current theory is that the main mechanism for the termination of signal produced by DA is via uptake into the presynatic terminal mediated by the dopamine transporter (I think diffusion also plays a significant role, but it probably depends on which brain regions you are discussing). The best example of a neurotransmitter which is predominantly terminated by metabolism would be acetylcholine and its degradation by acetylcholinesterase.

[quetzalcoatl9]

The best example of a neurotransmitter which is predominantly terminated by metabolism would be acetylcholine and its degradation by acetylcholinesterase.

For the OP: one real-life application of this is in pesticides. Most pesticides (i.e. non-metabolic) are inhibitors of acetylchline esterase; they covalently bind the Serine protease domain and permanent destroy the esterase activity of the enzyme. Since the acetylcholine is not being degraded, this creates a surplus of acetylchloline, leading to uncontrolled neural action.

[Math Is Hard]

Thanks, you brainy folks, for your responses. I appreciate it.

Moonbear, the book I am reading is an older version of Physiology of Behavior by Neil Carlson (http://www.amazon.com/exec/obidos/tg/detail/-/0205308406/qid=1121195543/sr=8-2/ref=sr_8_xs_ap_i2_xgl14/102-6470446-3456140?v=glance&s=books&n=507846)

hey Doc, this is probably a dumb question but what is the "DA" you referred to here:

.. although DA in the cleft is first hit by catechol-o-methyltransferanse (COMT)
quetzalcoatl9, that was an interesting example. Is this also how "nerve gas" works?

[quetzalcoatl9]

quetzalcoatl9, that was an interesting example. Is this also how "nerve gas" works?

yes, unfortunately.

[DocToxyn]

hey Doc, this is probably a dumb question but what is the "DA" you referred to here:


Sorry, MIH, I fell into my jargon and forgot to define the abbreviation, DA=dopamine. Nice observation about the nerve gas, sarin et al is nasty stuff!

[Math Is Hard]

Thanks for all the information, folks. Hopefully I can take a class in this one day.