NMDA channel

Under these conditions the fluorescence changes are caused by Ca 2+ permeating through NMDA channels.

Thus Mg ions block Ca channels (NMDA channels) for example, etc.

THE initial induction signal is a Ca 2+ transient which permeates NMDA channels.

The cooperativity threshold follows from the need for depolarization to reduce the level of the Mg 2+ block of the NMDA channel.

When many fibres are activated in synchrony by a 'strong' stimulus, depolarization spreads between neighbouring synapses to enhance the unblocking of NMDA channels.

This may involve phosphorylation of NMDA channels to alter the extent of the Mg 2+ block of these channels.

Through this site, reductants dramatically enhance NMDA channel activity, whereas oxidants either reverse the effects of reductants or depress native responses.

This combination of techniques has also enabled the Ca 2+ signal that permeates NMDA channels on dendritic spines to be detected (Fig. 2).

Though no further research has been done yet, it may also be involved with disrupted NMDA channels in the brain, which have both synergistic and regulatory effects on norepinephrine.

FIG. 2 Ca 2+ permeates NMDA channels to produce a transient signal in spines in response to tetanic stimulation.

Activation of the NMDA channel requires that glutamate and glycine bind at the same time to NR2 and NR1 subunits respectively.

The probable trigger for the induction of LTP is the entry of Ca 2+ through NMDA channels located on the postsynaptic cell.

Mg not only blocks the NMDA channel in a voltage-dependent manner but also potentiates NMDA-induced responses at positive membrane potentials.

But when the nerve cell receives signals from two other nerve cells at the same time, the NMDA channel springs open, allowing a current to flow into the cell.

It has also been reported to act on GABA-A and NMDA channels and to block T-type calcium channels.

In summary, the available evidence suggests that under normal conditions Ca 2+ permeates NMDA channels to provide a transient signal which is necessary for the induction of LTP.

There are indications from Ca 2+ imaging experiments that the Ca 2+ which permeates NMDA channels is augmented by Ca 2+ release from intracellular stores (see Box 3).

In contrast, little is known about the biochemical cascades that are triggered by the permeation of Ca 2+ through open NMDA channels and which lead to the persistent enhancement of synaptic efficiency.

Several different Ca 2+ -sensitive enzymes have been proposed to play a part in converting the probable induction signal, the entry of Ca 2+ through the NMDA channel, into persistent modifications of synaptic strength.

The phosphonate group of the NMDA antagonist binds to the glutamate-receptor, as does the natural agonist glutamic acid, but no conformational change that activates the NMDA channel occurs [ 28 ] .

Part of this signal depends on the synaptic activation of NMDA receptors and reflects, at least in part, Ca 2+ entry through NMDA channels and voltage-gated Ca 2+ channels.

LTP is thus localized at sites where NMDA channels are opened by active synaptic inputs that are releasing glutamate and causing depolarization of the postsynaptic cell, and will not affect nearby inactive synapses.

Because NMDA channels are permeable to Ca 2+ (refs 21, 38, 39) it is widely assumed, but not proven, that permeation through these channels during tetanic stimulation provides the Ca 2+ signal necessary for the induction of LTP.

This is because the tetanus maintains the neuron in a more depolarized state, which in turn reduces the extent of the Mg 2+ -induced block of NMDA channels, while at the same time providing the L-glutamate which promotes their opening.

It is likely that inositol 1,4,5-trisphosphate (InsP 3 ) generated as the result of the activation of mGluRs, as well as the Ca 2+ which permeates through NMDA channels, is involved in releasing Ca 2+ from intracellular stores.