title: Acid-sensing ion channel 1 and nitric oxide synthase are in adjacent layers in the wall of rat and human cerebral arteries.
abstract: Extracellular acidification activates a family of proteins known as acid-sensing ion channels (ASICs). One ASIC subtype, ASIC type 1 (ASIC1), may play an important role in synaptic plasticity, memory, fear conditioning and ischemic brain injury. ASIC1 is found primarily in neurons, but one report showed its expression in isolated mouse cerebrovascular cells. In this study, we sought to determine if ASIC1 is present in intact rat and human major cerebral arteries. A potential physiological significance of such a finding is suggested by studies showing that nitric oxide (NO), which acts as a powerful vasodilator, may modulate proton-gated currents in cultured cells expressing ASIC1s. Because both constitutive NO synthesizing enzymes, neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS), are expressed in cerebral arteries we also studied the anatomical relationship between ASIC1 and nNOS or eNOS in both rat and human cerebral arteries. Western blot analysis demonstrated ASIC1 in cerebral arteries from both species. Immunofluorescent histochemistry and confocal microscopy also showed that ASIC1-immunoreactivity (IR), colocalized with the smooth muscle marker alpha-smooth muscle actin (SMA), was present in the anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) and basilar artery (BA) of rat and human. Expression of ASIC1 in cerebral arteries is consistent with a role for ASIC1 in modulating cerebrovascular tone both in rat and human. Potential interactions between smooth muscle ASIC1 and nNOS or eNOS were supported by the presence of nNOS-IR in the neighboring adventitial layer and the presence of nNOS-IR and eNOS-IR in the adjacent endothelial layer of the cerebral arteries.
authors.affiliation: Department of Neurology, University of Iowa, Iowa City, IA 52242, USA. Electronic address: li-hsien-lin@uiowa.edu.
authors.forename: Li-Hsien
authors.initials: LH
authors.lastname: Lin
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Marcus B
authors.initials: MB
authors.lastname: Nashelsky
authors.affiliation: Department of Neurology, University of Iowa, Iowa City, IA 52242, USA; Neurology Service, Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Talman
mesh_terms: D062565:Acid Sensing Ion Channels / Q000032:analysis / Q000096:biosynthesis*; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D002102:Cadaver; D002536:Cerebral Arteries / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D062565:Acid Sensing Ion Channels; D019001:Nitric Oxide Synthase
keywords: Acid-sensitive ion channels; Cerebral artery; Human; Immunofluorescent histochemistry; Nitric oxide synthase; Western blot