Voltage-gated ion channel clustering on myelinated axons is controlled by glia

s39

MS06-3 KAZUHIDE

ATP

STIMULATES

CULTURED INOUEl,

CA2+-DEPENDENT

PLASMINOGEN

RELEASE

FROM

MICROGLIA

KAZUYUKI

NAKAJIMA2,

TAKAKO

MORIMOT02,

SHIZUYO

HONDA&

AND SHINICHI KOHSAKA2 ‘Division of Pharmacology, National Institute of Health Sciences, l-18-1 Kamiyoga, Setagaya, Tokyo 158, 2Deptiment of Neurochemistry, National Institute of Neuroscience, 4-l-l Ogawa-higashi, Kodaira, Tokyo 187, Japan We have reported that activated microglia release plasminogen which promotes the development of mesencephalic dopaminergic neurons and enhances neurite outgrowth. However, there is little evidence for the mechanism of plasminogen release from microglia. Since microglia express ATP receptors but not any glutamate receptors, we examined the effect of ATP on the release of plasminogen from microglia. ATP (lO-lOOpM), but not glutamate (IOOpM), stimulated the release of plasminogen from microglia in a concentration-dependent manner during a 10 min stimulation. A one hour pretreatment with BAPTA-AM (200 PM), completely inhibited the plasminogen release evoked by ATP. The Caz+ ionophore A23187 induced plasminogen release. ATP induced a transient increase in the intracellular calcium concentration ([Caz+]i) in a concentrationdependent manner similar to the ATP-evoked plasminogen release. The ATP-evoked increase in [Caz+]i was totally dependent on extracellular Ca2+. 2’-and 3’-0-(4-Benzoylbenzoyl)-adenosine S-triphosphate (BzATP), a selective agonist of P2X7, evoked a long-lasting increase in [Caz+]i stronger than ATP. One hour pretreatment with oxidized ATP(lOOpM), a selective antagonist of P2X7, blocked the increase in [Caz+]i by ATP. These data suggest that ATP causes an increase in [Caz+]i via the ionotropic P2X7 receptor which stimulates the release of plasminogen from the microglia.

MS06-4

A NOVEL ALLOSTERIC

IMASAYUKI SEKIGUCHI

Diseases, National Institute of Neuroscience,

glutamate receptors play an important

modulatory sites on AMPA receptors. tools when physiological

role in central excitatory synaptic transmission.

modulator

including those in neuron-glia

arc not matured

site on GABA receptors.

yet when compared

We recently

the chemical structure of previously with a theta pipette

receptor flop isoforms, receptors,

PEPA is a novel potentiator

MS06-5

recovery

desensitization

of AMPA receptors. have revealed

of AMPA receptors,

from desensitization

with studies

are investigated.

However,

about benzodiazepine

potentlator

sites, an

of AMPA receptors,

Electrophysiological

4-[2-

or a benzothiadiazine,

studies using outside-out

that PEPA preferentially

modulated

AMPA

showed only weak effects upon deactivation

in GluR3-flop

homomeric

of AMPA receptor with unique pharmacological

VOLTAGE-GATED ION CHANNEL CONTROLLED BY GLIA.

There are allosteric

(PEPA). PEPA is not a pyrrolidinone

driven by a piezo manipulator

suppressed

and facilitated

known potentiators

and

sites are useful as pharmacological

interactioo,

found a novel allosteric

(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide patches

: PEPA

National Center of Neurology

It seems that drugs which act on the modulatory

roles of AMPA receptors,

studies about the allosteric allosteric modulatory

OF AMPA RECEPTORS

and KEIJI WADA

Dept. of Degenerative Neurological Psychiatry. Kodaira, Tokyo 187 AMPA-type

POTENTIATOR

CLUSTERING

receptors.

These results

suggest

of the that

features.

ON MYELINATED

AXONS

IS

Hiroko Baba and Kazuhiro Ikenaka National Institute for Physiological Sciences, Okazaki 444-8585. The characteristic localization of ion channels is crucial for the propagation of saltatory conductions in myelinated nerves. For instance, the voltage-gated Na’ channels are located at node of Ranvier while the voltage-gated K’ channels are mainly found at juxtaparanodal regions. Recently a humoral factor secreted by oligodendrocytes has been reported to induce clustering of Na’ channels at nodes of Ranvier (Kaplan et al, 1997). In contrast, our studies showed that the K’ channel clustering was well correlated with the formation of myelin sheaths on the axons, but not with the association of oligodendrocyte processes, suggesting that formation of the compact myelin is important for K’ channel clustering. During myelination processes, the humoral factor secreted from oligodendrocyte may facilitate Na’ channel clustering with the intervals similar to those with nodes of Ranvier, oligodendrocyte processes then find the place to myelinate between these clusters, and finally after the myelin sheaths are formed and some signals are sent to the axons, K’ channels may form clusters near the paranodal loops of myelin membrane. Thus, changes of channel localization during myelination process represents dynamic interactions between neuron and glia.