-1 Receptor Modulation of Acid-Sensing Ion Channel a (ASIC1a) and ASIC1a-Induced Ca2 Influx in Rat Cortical Neurons

Acid-sensing ion channels (ASICs) are proton-gated cation channels found in peripheral and central nervous system neu-rons. The ASIC1a subtype, which has high Ca2 permeability, is activated by ischemia-induced acidosis and contributes to the neuronal loss that accompanies ischemic stroke. Our lab-oratory has shown that activation of receptors depresses ion channel activity and [Ca2]i dysregulation during ischemia, which enhances neuronal survival. Whole-cell patch-clamp electrophysiology and fluorometric Ca2 imaging were used to determine whether receptors regulate the function of ASIC in cultured rat cortical neurons. Bath application of the selective ASIC1a blocker, psalmotoxin1, decreased proton-evoked [Ca2]i transients and peak membrane currents, suggesting the presence of homomeric ASIC1a channels. The pan-selectiv