jatkuu..Glutaminerginen hermotus. Interneuroni ja pyramidaalisolu. NMDAr

Glutaminergisen hermojärjestelmän alueelta jälleen pientä tiedon laajenemaa.
Tässä väitöstyössä mainitaan myös erikseen mihin kohtaan vaikuttaa memantine molekyyli, joka kuuluu Alzheimerin taudin lääkeaineisiin.

LÄHDE: Ilse Riebe. Differences in glutamatergic transmission unto interneurons and pyramidal cells of the rat hippocampus. University of Gothenburg (20109 ISBN978- 91- 628-8152-8

Suomennan abstraktista ja myös muusta sisällöstä hieman.
(Abstrakti suomennettu edelllä)
Tutkija kirjoitaa näin:
Tonic excitation via extrasynaptic NMDAr has been less studied.

Interneurons have larger tonic NMDAr mediated currents at negative membrane potentials than pyramidal cells.

These tonic NMDAr mediated currents were inhibited to 50% of control by 10 uM of the NMDAreceptor open channel blocker MEMANTINE, a medicine used in Alzheimer disease.

NMDA receptors
are present in the neuronal membrane either extrasynaptically OR clustered in the postsynaptic membrane= synaptic NMDA receptor.(Lau et Zukin, 2007; Croc et al. 2009) .

Extrasynapic NMDAr have been shown to open as a consequence of glutamate spill over from synapses during bursts of synaptic activation (Arnth, Jense et al. 2002).

CA1 pyramidal cells.
They can also be tonically activated by ambient concentration of agonists (Sak et al. 1989).

NMDAr open channel blockers are used clinically for treatment of Alzheimer disease or experimentally as a made model of schizophrenia(Gaspar et al 2003).

Memantine = magnesium mimicking, readily reversible open channel blocker of the NMDA receptor channel.It is said to improve kognitition function in Alzheimer disease (Parsons et al. 2007) How is it possible such a paradox, because NMDAr are necessary for the induction of LT synaptic plasticity.


...

This low concentration of Memantine did not affect synaps i NMDAr mediated responses neither in interneurons, nor in pyramidal cells.

Memantine 10 uM reduces the disynaptic/PSC in pyramidal cells
and increased the magnitude of population spike so that tonically active extrasynaptic NMDAr contribute to intrinsic excitation, particularly in interneurons,

and that these NMDArs are specifically targeted by low doses of NMDAr open channel blockers.

Possible low concentration of NMDAr antagonists disinhibit glutamateergic principal cells This facilitates LTP induction. (1983).

It has been speculated that synaptic NMDAr on GABAergic interneurons are more suspectible to these antagonists than synaptic NMDArs on principal cells (Lisman 2008).
(There i no evicence about this).

Or:
The extrasynaptic NMDAr are more sensitive to these antagonists than synaptic receptors are and they are expressed on higher density on interneurons than on principal cells.

Recent studies have indicated that the GABAergic interneurons express tonically active extrasynaptical NMDAr of both physiological and pathophysiological importance ( Look the article Mann et Mode 2010; Milnerwood et al.)