Disease relevance of Accn2

• In focal ischemia, intracerebroventricular injection of ASIC1a blockers or knockout of the ASIC1a gene protects the brain from ischemic injury and does so more potently than glutamate antagonism [1].
• In contrast, ASIC1 knockouts develop hyperalgesia similar to their wildtype littermates [2].
• ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons [3].
• We found that extracellular acidosis elicited a greater current density in amygdala neurons than hippocampal neurons and that disrupting the ASIC1 gene eliminated H+-evoked currents in the amygdala [4].
• These findings further suggest that ASIC1a is a novel molecular target involved in ischaemic brain injury [5].
• Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone [6].

Psychiatry related information on Accn2

• These data raise the possibility that ASIC1a and H(+)-gated currents may contribute to the development of abnormal fear and to anxiety disorders in humans [7].

High impact information on Accn2

• Cells lacking endogenous ASICs are resistant to acid injury, while transfection of Ca2+ -permeable ASIC1a establishes sensitivity [1].
• CONCLUSIONS: ASIC1 influences visceral but not cutaneous mechanoreceptor function, suggesting that different mechanisms underlie mechanosensory function in gut and skin [8].
• The role of ASIC1 is highlighted by prolonging gastric emptying of a meal in ASIC1-/- animals [8].
• RESULTS: ASIC1 was expressed in sensory ganglia and was lost after disruption of the ASIC1 gene [8].
• The results show that acid-sensitive channels are expressed in midbrain dopamine neurons and suggest that ammonium sensitivity is a widely distributed ASIC characteristic in the CNS, including the hippocampus [9].

Chemical compound and disease context of Accn2

• In cultured dorsal root ganglion neurons, whole cell patch clamp recordings showed that the majority of capsaicin-sensitive rat dorsal root ganglion neurons displayed large proton-evoked inward currents with transient ASIC-like properties [10].
• Attenuating brain acidosis by NaHCO3 or blocking ASIC1a with PcTX were both protective [5].

Biological context of Accn2

• Coexpression of p11 and ASIC1a in CHO-K1 cells led to a 2-fold increase in expression of the ion channel at the cell membrane as determined by membrane-associated immunoreactivity and cell-surface biotinylation [11].
• In addition, ASIC1-/- mice showed almost double the gastric emptying time of wild-type mice [8].
• Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis determined expression of ASIC1 messenger RNA and protein in vagal and spinal sensory ganglia [8].
• Kinetics is similar for ASIC1b and ASIC1a [12].
• Acidification-induced action potentials in these neurons were compatible in a pH-dependent manner with the pH dependence of ASIC-like current [13].

Anatomical context of Accn2

• Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3 [14].
• METHODS AND RESULTS: Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes [14].
• These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera [14].
• Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and 3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal root ganglia [15].
• The acid-sensing ion channel 1a (ASIC1a) is abundantly expressed in the amygdala complex and other brain regions associated with fear [7].

Associations of Accn2 with chemical compounds

• These data demonstrate that p11, already known to traffic members of the voltage-gated sodium and potassium channel families as well as transient receptor potential and chloride channels, also plays a selective role in enhancing ASIC1a functional expression [11].
• We have recently demonstrated that ASIC function is regulated by serine proteases [16].
• Ca(2+) permeability of ASIC1a is low, whereas ASIC1b is impermeable to Ca(2+) [12].
• Site-directed mutagenesis studies identified involvement of cysteine 61 and lysine 133, located in the extracellular domain of the ASIC1a subunit, in the modulation of ASICs by oxidizing and reducing agents, respectively [17].
• Modulation of Acid-sensing Ion Channel Currents, Acid-induced Increase of Intracellular Ca2+, and Acidosis-mediated Neuronal Injury by Intracellular pH [18].

Other interactions of Accn2

• However, the specific contribution of ASIC1 and ASIC2 subunits to acid-evoked currents in hippocampal neurons remained uncertain [19].
• ASIC1 was enriched in areas with strong excitatory synaptic input such as the glomerulus of the olfactory bulb, whisker barrel cortex, cingulate cortex, striatum, nucleus accumbens, amygdala, and cerebellar cortex [4].

Analytical, diagnostic and therapeutic context of Accn2

• AIMS: Members of the acid sensing ion channel (ASIC) family are strong candidates as mechanical transducers in sensory function [14].
• Localization of ASIC expression in DRG was determined with fluorescence in situ hybridization (FISH) and retrograde tracing [15].
• We determined relative expression of ASIC1, 2, and 3 in mouse thoracolumbar dorsal root ganglia (DRG) by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis (QPCR) and specifically in retrogradely traced colonic neurons isolated via laser capture microdissection [15].
• The amygdala showed prominent expression, and overexpressing ASIC1a enhanced fear conditioning, an animal model of acquired anxiety [7].
• Reverse transcriptase-nested PCR and Western blotting showed that three ASIC isoforms, ASIC1a, ASIC2a, and ASIC2b, are expressed at a high level in dorsal horn neurons [13].

References