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So returning to outline,
we see that sodium is highly conserved in class A GPCRs,
brazenly highly conserved, We see that it participates as
a switch in the conformational changes upon activation on the receptor.
So it is highly involved in function of receptor and revolution conserve dysfunction.
So it suppose to be very important for the whole family.
Now that we have put aside that sodium was a key factor in GPCRs signaling mechanism.
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There are some indications,
again from both physical studies,
biochemical studies in vitro.
In this particular work from year 2,000.
It shows that first of all,
increasing concentration of sodium decreases quite profoundly the basal attitudes.
So it stops receptor from spontaneous signaling and on the bottom panel
it also show that it actually enhances or
promotes the response of the receptor to full agonists.
In this particular case,
for the Mu Opioid receptor,
basically, if you look at the zero concentration of sodium,
there is almost no difference in full agonists and partial agonists simulation
of GTPS binding and while the sodium concentration increases,
it allows to differentiate that into full agonists and partial agonists,
through which indicates that presence of
sodium modulates and enhances signaling effects of wagons.
This is from earlier study as well comparing
all basal activity with full agonists and antagonists signaling,
in this case in GTPs activity.
What is important in this experiment,
it was done with keeping down extreme the same and exchanging sodium to potassium.
What happens is with increase concentration of sodium,
the basal activity dramatically reduce that we've seen in the previous example.
But full agonists signaling does not.
So again, it differentiates between basal activity and the full agonist activity.
So it enhances the signaling by the full agonists.
