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Neural Plasticity
Volume 2016 (2016), Article ID 1239629, 7 pages
Research Article

Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

Department of Health and Biomedical Sciences, The University of Texas Rio Grande Valley, One West University Boulevard, Brownsville, TX 78520, USA

Received 11 June 2015; Revised 15 September 2015; Accepted 16 September 2015

Academic Editor: Clive R. Bramham

Copyright © 2016 Masako Isokawa. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium () and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing . A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust -independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.