title: Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system.
abstract: The acid-sensitive ion channel ASIC1 is a proton-gated ion channel from the mammalian nervous system. Its expression in sensory neurons and activation by low extracellular pH suggest that ASIC is involved in transmitting nociceptive impulses produced by the acidification caused by injury or inflammation. However, ASIC1 expression is not restricted to sensory neurons. To understand the functional role of ASIC1 in the CNS we investigated its expression and subcellular distribution therein. In particular, we examined the presence of ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under physiological conditions. Immunostaining with specific antibodies revealed broad expression of ASIC1 in many areas of the adult rat brain including the cerebral cortex, hippocampus and cerebellum. Within cells, ASIC1 was found predominantly throughout the soma and along the branches of axons and dendrites. ASIC1 was not enriched in the microdomains where pH may reach low values, such as in synaptic vesicles or synaptic membranes. Pre- or postsynaptic ASIC1 was not gated by synaptic activity in cultured hippocampal neurons. Blockage or desensitization of ASIC1 with amiloride or pH 6.7, respectively, did not modify postsynaptic currents. Finally, the ontogeny of ASIC1 in mouse brain revealed constant levels of expression of ASIC1 protein from embryonic day 12 to the postnatal period, indicating an early and almost constant level of expression of ASIC1 during brain development.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Krueger
authors.forename: Annette
authors.initials: A
authors.lastname: Kolar
authors.forename: Deren
authors.initials: D
authors.lastname: Shao
authors.forename: Reiko Maki
authors.initials: RM
authors.lastname: Fitzsimonds
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Canessa
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D000906:Antibodies / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000276:immunology / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014018:Tissue Distribution
chemical_list: C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D000906:Antibodies; C568268:Asic1 protein, rat; D015415:Biomarkers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels