Modulation of Neurotransmission by Acid-Sensing Ion Channels

Interstitial pH fluctuations occur normally in the brain and significantly modulate neuronal functions. Acid-sensing ion channels (ASICs), which serve as neuronal acid chemosensors, play important roles in synaptic plasticity, learning, and memory. However, the specific mechanisms by which ASICs influence neurotransmission remain elusive. Here, we report that ASICs modulate transmitter release and axonal excitability at a glutamatergic synapse in the rat and mouse hippocampus. Blocking ASIC1a channels with the tarantula peptide psalmotoxin 1 down-regulates basal transmission and alters short-term plasticity. Notably, the effect of psalmotoxin 1 on ASIC-mediated modulation is age-dependent, occurring only during a limited postnatal period (postnatal weeks 2-6). This finding suggests that protons, through the activation of ASICs, may act as modulators in synapse formation and maturation during early development.