Acid-Sensing Ion Channel 1a Is Involved in N-Methyl D-Aspartate Receptor-Dependent Long-Term Depression in the Hippocampus.

D Mango,R Nisticò

doi:10.3389/fphar.2019.00555

Abstract

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are largely expressed in the mammalian nervous system. ASIC1a is highly permeable to Ca2+ and are involved in many physiological processes, including synaptic plasticity, learning, and memory. To clarify the role of ASIC1a in synaptic transmission and plasticity, we investigated N-methyl D-aspartate (NMDA) receptor-dependent long-term depression (LTD) in the CA1 region of the hippocampus. We found that: (1) ASIC1a mediates a component of ASIC1a excitatory postsynaptic currents (EPSCs); (2) ASIC1a plays a role in electrical LTD induced by LFS protocol both in P13-18 and P30-40 animals; (3) ASIC1a is involved in chemical LTD induced by brief bath application of NMDA both in P13-18 and P30-40 animals; and finally (4) a functional interaction between ASIC1a and NMDA receptors occurs during LTD. These findings suggest a new role for ASIC1a in specific forms of synaptic plasticity in the mouse hippocampus.

Highlights

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are largely expressed in the mammalian nervous system (Waldmann et al, 1997a)
In order to assess whether ASIC1 contributes to basal excitatory transmission, we recorded excitatory postsynaptic currents (EPSCs) elicited by stimulation of the Schaffer collaterals fibers in the presence of PcTx-1, a polypeptide from the venom of spider toxin, that inhibits homomeric ASIC1a currents (Escoubas et al, 2000)
We have demonstrated that ASIC1a contributes, to a small extent, to basal excitatory postsynaptic currents in CA1 pyramidal neurons

Summary

Introduction

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are largely expressed in the mammalian nervous system (Waldmann et al, 1997a). Extracellular acidification occurs in the brain during many different physiological and pathological situations as elevated neural activity, increased metabolism, and neuronal injury. Several works suggested that the acidic pH of synaptic vesicles transiently influences local extracellular pH during neurotrasmitters release (Krishtal et al, 1987; Waldmann et al, 1997b). According with this idea, it has been demonstrated that transient acidification of extracellular pH occurs in synaptic transmission in cultured hippocampal neurons (Miesenböck et al, 1998) and in

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