Commentary Cell Science Reviews Vol 6 No 3 ISSN 1742-8130

Acid sense and sensibility in the amygdala

Acid sensing ion channels (ASICs) are non-selective cation channels gated by a fall in extracellular pH (pHe). In the brain, targeted knock out studies have implicated ASICs in synaptic plasticity as well as spatial memory, and fear-conditioned behavior. This work pointed strongly toward a role for ASICs in the function of the hippocampus and amygdala, but how the proposed roles for ASICs relate to brain pHe is unclear. The functional link of brain ASICs to pHe was strengthened by a recent study that correlated ASIC1a subunit expression in the amygdala with CO2-mediated accentuation of fear-related behavior. Whether brain ASICs are otherwise gated by changes in pHe is unknown. Putative rapid extracellular acid shifts that might effectively gate ASICs remain hypothetical in both the hippocampus and amygdala. Indeed, in hippocampus, neural activity results in a fast alkaline transient, while the behavior of pHe in the amygdala is unexplored. There is evidence that alkaline transients in hippocampus are especially large within a synaptic microdomain. Similarly, large acidic shifts could be plausible within discrete extracellular domains, perhaps associated with ASICs. A variety of membrane transporters in concert with extracellular carbonic anhydrases could act to shape such local pHe responses. Thus, the intriguing recent work on ASIC1 knock out mice should fuel exciting new studies to untangle the relationship between pHe, ASICs, and other H⁺-sensitive channels in the amygdala, as well as in other regions of the brain.

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