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

الملخص EN

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.