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Science 289 (5478): 460-463

Copyright © 2000 by the American Association for the Advancement of Science

The Role of GTP-Binding Protein Activity in Fast Central Synaptic Transmission

Tomoyuki Takahashi,* Tetsuya Hori, Yoshinao Kajikawa, Tetsuhiro Tsujimoto

Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved in exocytosis, endocytosis, and recycling of vesicles in yeast and mammalian secretory cells. However, little is known about their contribution to fast synaptic transmission. We loaded guanine nucleotide analogs directly into a giant nerve terminal in rat brainstem slices. Inhibition of G-protein activity had no effect on basal synaptic transmission, but augmented synaptic depression and significantly slowed recovery from depression. A nonhydrolyzable GTP analog blocked recovery of transmission from activity-dependent depression. Neither effect was accompanied by a change in presynaptic calcium currents. Thus, G proteins contribute to fast synaptic transmission by refilling synaptic vesicles depleted after massive exocytosis.

Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan.
*   To whom correspondence should be addressed. E-mail: ttakahas-tky{at}umin.ac.jp

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