Biphasic action of axonal GABA-A receptors on presynaptic calcium influx.

Although ionotropic γ-aminobutyric acid A receptors (GABA(A)Rs) have long been known to exist on the axons of many different cells, their effect on axon excitability and synaptic transmission remains controversial. Here, using high-speed Ca(2+) imaging, it is shown that they induce a biphasic effect in parallel fibers of the cerebellar cortex. Multicellular measurements indicate a facilitation of action potential (AP)-evoked Ca(2+) transients, which is subsequently followed by depression. However, the receptor activation does not increase influx of Ca(2+) into individual fibers but instead, increases the probability of AP generation. These results provide a description of the effect of presynaptic GABA(A)R activation and explain why reports of the effect of their activation have been so varied.