LAUSR

Acid-sensing ion channels (ASICs) participate in synaptic transmission due to acidic content of synaptic vesicles, but their contribution in the postsynaptic currents is small. This stimulates attempts to find endogenous ASIC potentiators that could enhance ASIC-mediated currents to physiologically relevant values. Here we demonstrate that glutamate that serves as neurotransmitter, potentiate recombinant ASIC1a in submillimolar concentrations. The effect of glutamate is especially interesting as ASIC's presence have been shown in glutamatergic synapses. At pH = 6.5 glutamate had maximum potentiation of 87% with EC50 value of 0.65 mM. The mechanism of potentiation is the shift of activation pH-dependence to less acidic values, with 0.5 mM glutamate increasing pH50 from 6.04 to 6.43. This way ASIC1a in glutamatergic synapses might be intrinsically potentiated. Furthermore, this effect could compensate for the inhibition of ionotropic glutamate receptors by extracellular acidification during synaptic transmission. This article is protected by copyright. All rights reserved.