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Neuron function question

Matthew Kirkcaldie Matthew.Kirkcaldie at deletethis.newcastle.edu.au
Sun Oct 26 20:21:48 EST 2003

In article <0tbmb.167318$6C4.167192 at pd7tw1no>,
 "David Todtman" <dtodtmanREMOVETHHIS at shaw.ca> wrote:

> I am trying to understand an element of neuron action.
> At the outset, I want to thank anyone who takes the time to help me out
> here.

At the risk of being irrelevant, I thought I would try to add my own 
simple answers to these queries.  Much excellent information has already 
been provided by some of the wise heads here, but I always think it's 
worth hearing several different explanations - different ways of 
expressing the same thing can make sense to different people!

> The text I am using notes two types of neuronal action:  ionic and
> metabolic.  An ionic action occurs when enough neurotransmitter molecules
> (or other ligands) bind with postsynaptic cell receptors.  I gather that the
> binding is an electro-chemical bond and when enough electro-chemical bonds
> occur, the electrical potential of the postsynaptic cell changes rapidly and
> the cell is said to "fire."  Is this more or less the general idea?  I do
> not have to understand this process in a deeply technical way.

In this type of synaptic transmission, bonding between transmitter and 
receptor causes the receptor to open (often by "untwisting") and permit 
some kinds of dissolved ions to pass through the membrane more easily.  
Since the neuron spends a lot of energy maintaining their "resting 
potential" (an imbalance between the contents of the cell and the 
extracellular fluid), opening channels like this can cause the resting 
potential to become disturbed, if the ions permitted through are of the 
right type.  (It can also lead to a restoration of the membrane 
potential - this is what happens with inhibitory transmitters which 
prevent the neuron from firing.)

If this disturbance (depolarization) reaches the sensitive region at the 
start of the axon, it triggers a local feedback process by opening still 
more ion channels.  This disturbance propagates quickly along the 
membrane, and is called the action potential, which has been "fired" by 
a depolarization of sufficient size.  Of course, at the other end of the 
axon, this action potential causes neurotransmitter release to 
communicate to another cell, usually a neuron or a muscle cell.

> Now for a second question.  The text says that metabolic actions occur
> gradually--hours, days, weeks, or months.  Then, the text says, "When
> ligands bind to these receptors, they operate by activating what are
> referred to as _second messenger systems_ within the cytoplasm of the cell."
> What is not explained in the text is "these receptors."  Are there a
> specific class of receptors that are 'metabolic receptors' as opposed to
> 'ionic receptors'?

Yes, this is exactly right.  The types are known as "ionotropic" and 
"metabotropic" receptors respectively.  Often receptors of both classes 
exist for a given neurotransmitter, for example the GABA-A receptor is 
ionotropic (lets through chloride ions to restore the membrane 
potential) whereas the GABA-B receptor is metabotropic (causes changes 
to the neuron's biochemistry and gene expression).  This allows 
transmitters to have an immediate effect as well as long-term effects.  
Some of the reasons for the time delay are transporting the molecules 
back to the nucleus, and the time taken to manufacture and transport the 
proteins which have been stimulated.

> Now, here is another query.  The text says that the second messenger systems
> within the alter the cell's internal chemical environment.  Okay but what
> specifically are the "messengers"?   Particular molecules?  Do the these
> ligands pass into the cell thus altering the internal environment?

The second messengers are molecules, already inside the cell, which are 
activated by the ligand binding to the receptor on the outside of the 
neuron - it never actually comes in (and nor does it with the ionotropic 
receptors).  The nature of the second messenger depends on the receptor 
and how the receptors are grouped together (they influence each other), 
but it's generally of the form of an activated enzyme which causes 
changes to other proteins in the nearby region, and may also pass back 
to the nucleus and change which genes are being transcribed and which 
proteins are being made.  The activation process occurs via a 
biochemical cascade which involves G-proteins and, usually, release of 
calcium from internal storage.  Where the activated enzymes go depends 
on what type of molecules they are, and whether they can be transported 
by the various systems in the neuron.

> And finally, one result of metabolic action can be alteration in the number
> of receptor cites.  In simple terms, what are some ways that this may occur?
> I.e., I believe that receptors are protein structures and does it happen
> that a type of metabolic action results in reductions in the cell's ability
> to manufacture the receptors?

That can occur, or more receptors can be "ordered" from the nucleus.  A 
lot of it happens by surprisingly direct means - certain enzymes can 
cause nearby bits of membrane to be sucked back inside the cell, taking 
receptors with them, so there are fewer at the surface to take part in 
synaptic transmission.  These "internalised" receptors can also be 
replaced back in the membrane if other biochemical signals are 
activated.  Often these types of events depend on how much activity has 
recently occurred at the synapse, rather than just one synaptic 
transmission.  Glutamate receptor addition and removal at a synapse are 
called "long term potentiation" and "long term depression" respectively, 
and have been intensively studied over the last 20 years.

Of course, the real point of these types of systems is that the 
structure of a neuron changes according to the activity of its synapses, 
which means that the nervous system alters itself depending on the 
experience it receives, and how that experience compares with its 
internal activity.  That's what the nervous system is for!

Hope that helps.



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