Barium evokes glutamate release from rat brain synaptosomes by membrane depolarization: involvement of K+, Na+, and Ca2+ channels.
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 microM. 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 Ba(2+)-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+.
Sihra
T S
TS
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129.
Piomelli
D
D
Nichols
R A
RA
D000818:Animals; D001464:Barium / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007425:Intracellular Membranes / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D015222:Sodium Channels / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism* / Q000502:physiology*
D015220:Calcium Channels; D005971:Glutamates; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D015222:Sodium Channels; D001464:Barium; D018698:Glutamic Acid