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Bill Skaggs bill at nsma.arizona.edu
Fri Nov 5 16:02:24 EST 1993

markb at orl.mmc.com (Mark Bower) writes:

   William White asked
   > I was under the impression that glycine was required for the NMDA channel
   > to operate.  Is this in fact true?

   From Z. Hall's _Introduction to Molecular Neurobiology_, 1992, Sinauer,
   "The NMDA receptor also has an unusual form of voltage-regulation in which
   the open channel is occluded ar normal resting potential by magnesium ion in
   the extracellular fluid. Depolarization drives the magnesium ion out of the
   channel, allowing other ions to pass. Thus, glutamate is most effective in
   opening the NMDA channel when the cell is depolarized."

   The answer would appear to be magnesium, not glycine, is required. Unless I
   misunderstood the question and you were talking about a specific part of the
   protein sequence in the NMDA channel.

Glutamate, glycine, magnesium, and postsynaptic membrane potential are
*all* involved in the workings of the NMDA receptor -- probably a
number of other factors as well.  Let me see if I can put this in
understandable terms:

1) Under ordinary conditions, the NMDA receptor opens (and allows
current flow) when glutamate is present AND the postsynaptic membrane
is depolarized.

2) These "ordinary conditions" include a reasonably high extracellular
concentration of glycine and a reasonably high intracellular
concentration of magnesium.

3) If there is no extracellular glycine, current flow through the NMDA
channel will be drastically reduced even when glutamate and
postsynaptic depolarization are present.  

4) If there is no intracellular magnesium, then glutamate alone is
sufficient to cause current flow -- postsynaptic depolarization is no
longer necessary.  (Ordinarily, glutamate opens the channel but it
gets clogged by magnesium ions unless there is enough postsynaptic
depolarization to pull the magnesium away from the channel opening.)

If you speak C,

  Current = Glutamate && (Depolarization || !Magnesium) && Glycine;

	-- Bill

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