title: Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity.
abstract: 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 ([Ca(2+)]i) 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 [Ca(2+)]i. 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 [Ca(2+)]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a [Ca(2+)]i 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 Ca(2+)-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.
authors.affiliation: Department of Health and Biomedical Sciences, The University of Texas Rio Grande Valley, One West University Boulevard, Brownsville, TX 78520, USA.
authors.forename: Masako
authors.initials: M
authors.lastname: Isokawa
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002110:Caffeine; D005680:gamma-Aminobutyric Acid