Presynaptic released protons act as neurotransmitters activating acid sensing ion channels 1a (ASIC-1a) which modulate synaptic transmission and plasticity at the mouse calyx of Held

MARIANO N. DI GUILMI; FRANCISCO J. URBANO; CARLOTA GONZÁLEZ INCHAUSPE; OSVALDO D. UCHITEL

Ciudad Autonoma de Buenos Aires

Congreso; 2nd FALAN Congress (Federación de Sociedades de Neurociencias de Latinoamérica y el Caribe).; 2016

FALAN (Federación de Sociedades de Neurociencias de Latinoamérica y el Caribe).

Increase in proton concentration or reduction in pH occursin both physiological and disease conditions activating acid-sensing ionchannels (ASICs). We found that homomeric ASIC-1a channels sensitive to PcTx1 canbe activated in postsynaptic neurons of the medial nucleus of the trapezoidbody (MNTB) of the auditory system, inducing transient inward currents (IASIC)during exogenous H+ application in wild type (WT) mice. We alsodetect ASIC1a-dependent currents during synaptic transmission, suggesting anacidification of the synaptic cleft due to the co-release of neurotransmitterand H+ from synaptic vesicles. ASIC-1a channels are permeable to Ca2+. Activation of ASIC-1ain MNTB neurons by exogenous H+ induces an increase in intracellularCa2+.  Furthermore, highfrequency stimulation (HFS) of the presynaptic nerve terminal leads to aPcTx1-sensitive increase in [Ca2+] in MNTB neurons. During HFS,synaptic transmission shows increased short term depression (STD) ofglutamatergic excitatory postsynaptic currents (EPSCs) in MNTB neurons fromASIC1a-/- compared to WT mice. These results suggest thatpresynaptic released protons acting as co-transmitters are relevant to modulatetransmitter release by activating ASIC-1a channels at the calyx of Held-MNTBsynapse. Postsynaptic ASIC-1a channels contribute to neurotransmissionmodifying intracellular Ca2+ and modulating synaptic strength andshort term plasticity (STP). Changes in STP may affect cognitive function inASIC1 knockout mice, taking into account that ASIC1 channels are involved inlearning and memory, and play important roles in neurodegenerative diseases.