The present address of Dr. T. A. Sihra is the Department of Pharmacology, Royal Free Hospital School of Medicine, University of London, London NW3 2PF, U.K.
Barium Evokes Glutamate Release from Rat Brain Synaptosomes by Membrane Depolarization: Involvement of K+, Na+, and Ca2+ Channels
Article first published online: 15 DEC 2006
Journal of Neurochemistry
Volume 61, Issue 4, pages 1220–1230, October 1993
How to Cite
Sihra, T. S., Piomelli, D. and Nichols, R. A. (1993), Barium Evokes Glutamate Release from Rat Brain Synaptosomes by Membrane Depolarization: Involvement of K+, Na+, and Ca2+ Channels. Journal of Neurochemistry, 61: 1220–1230. doi: 10.1111/j.1471-4159.1993.tb13612.x
The present address of Dr. D. Piomelli is the Unite de Neurobio-logie de 1′TNSERM, Centre Paul Broca, 75014 Paris, France.
- Issue published online: 15 DEC 2006
- Article first published online: 15 DEC 2006
- Received September 23, 1992; final revised manuscript received January 15, 1993; accepted February 5, 1993
- Neurotransmitter release;
- Ion channels
Abstract: During K+ -induced depolarization of isolated rat brain nerve terminals (synaptosomes), 1 mM Ba2+ could substitute for 1 mM Ca2+ in evoking the release of endogenous glutamate. In addition, Ba2+ was found to evoke glutamate release in the absence of K+-induced depolarization. Ba2+ (1–10 mM) depolarized synaptosomes, as measured by voltage-sensitive dye fluorescence and [3H]-tetraphenylphosphonium cation distribution. Ba2+ partially inhibited the increase in synaptosomal K+ efflux produced by depolarization, as reflected by the redistribution of radiolabeled 86Rb+. The release evoked by Ba2+ was inhibited by tetrodotoxin (TTX). Using the divalent cation indicator fura-2, cytosolic [Ca2+] increased during stimulation by approximately 200 nM, but cytosolic [Ba2+] increased by more than 1 μM. Taken together, our results indicate that Ba2+ initially depolarizes synaptosomes most likely by blocking a K+ channel, which then activates TTX-sensitive Na+ channels, causing further depolarization, and finally enters synaptosomes through voltage-sensitive Ca2+channels to evoke neurotransmitter release directly. Though Ba2+-evoked glutamate release was comparable in level to that obtained with K+-induced depolarization in the presence of Ca2+, the apparent intrasynaptosomal level of Ba2+ required for a given amount of glutamate release was found to be several-fold higher than that required of Ca2+.