Disease relevance of Accn2

• The patterns of expression of ASIC and ASIC-beta transcripts in rat dorsal root ganglion neurons are distinct [1].
• Here, we show that acidosis activates Ca2+ -permeable acid-sensing ion channels (ASICs), inducing glutamate receptor-independent, Ca2+ -dependent, neuronal injury inhibited by ASIC blockers [2].
• An analysis of the promoter region of the ASIC3 encoding gene, an ASIC specifically expressed in sensory neurons and associated with chest pain that accompanies cardiac ischemia, reveals that gene transcription is controlled by NGF and serotonin [3].

High impact information on Accn2

• Here we show that lactate, acting through extracellular divalent ions, dramatically increases activity of an acid-sensing ion channel (ASIC) that is highly expressed on sensory neurons that innervate the heart [4].
• Here we show that acid-sensing ion channel 3 (ASIC3), but no other known acid-sensing ion channel, reproduces the functional features of the channel that underlies the large acid-evoked current in cardiac afferents [5].
• pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits [6].
• Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1) [7].
• This paper describes a novel 40-amino acid toxin from tarantula venom, which potently blocks (IC(50) = 0.9 nm) a particular subclass of ASIC channels that are highly expressed in both central nervous system neurons and sensory neurons from dorsal root ganglia [8].

Biological context of Accn2

• Our results indicate that ASIC1b is an effective sensor of transient H(+) signals during slight acidosis and that, in addition to alternative splicing, interaction with di- and polyvalent cations extends the dynamic range of ASIC H(+) sensors [7].
• A-317567 produced concentration-dependent inhibition of all pH 4.5-evoked ASIC currents with an IC50 ranging between 2 and 30muM, depending upon the type of ASIC current activated [9].
• Klenow fragment-mediated labeling of DNA strand breaks determined that ASIC 2a induction did not occur in cells with detectable DNA damage [10].
• Western blot analysis with an anti-ASIC 2a antibody revealed up-regulation of an 80 kD protein in ischemic rat brain [10].
• Activation of the hippocampal ASIC-like current by a pH drop to 6.9 or 6.6 induces a transient depolarization which itself triggers an initial action potential (AP) followed by a sustained depolarization and trains of APs [11].

Anatomical context of Accn2

• Two proton-gated channels, acid-sensing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are members of the amiloride-sensitive ENaC/Degenerin family are known to be expressed by sensory neurons [1].
• In sensory neurons ASIC1 may constitute a nociceptor for pain induced by local acidification, whereas in central neurons it may modulate synaptic activity [12].
• Within cells, ASIC1 was found predominantly throughout the soma and along the branches of axons and dendrites [13].
• Immunostaining with specific antibodies revealed broad expression of ASIC1 in many areas of the adult rat brain including the cerebral cortex, hippocampus and cerebellum [13].
• ASIC1 was not enriched in the microdomains where pH may reach low values, such as in synaptic vesicles or synaptic membranes [13].

Associations of Accn2 with chemical compounds

• Neuropeptide FF (NPFF) and FMRFamide have been shown to potentiate proton-gated currents from cultured sensory neurons and acid sensing ion channel (ASIC) cDNA transfected cells [14].
• The EC50 and Hill coefficient for the activation of ASIC-like currents by protons are not affected by DTT [15].
• Zn(2+) increases the acid sensitivity of ASIC channels, and consequently neuronal excitability [11].
• We suggest that the pH dependence of the modulatory action of RFa-related peptides can be associated with the interaction of a positively charged arginine with histidine residues in the molecule of ASIC [16].
• In decerebrate rats (n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker) [17].

Regulatory relationships of Accn2

• In particular, we examined the presence of ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under physiological conditions [13].
• Recently, others have shown that the neurotrophic factor NGF stimulates expression of acid-sensing ion channel molecules, which are members of the DEG/ENaC family [18].

Other interactions of Accn2

• We have now identified MDEG1 as a proton-gated channel with properties different from those of ASIC [19].
• Acid-sensing ion channel (ASIC) and transient receptor potential/vanilloid receptor subtype-1 (TRPV1) encode proton-activated cation channels expressed by nociceptors and the opening of these channels results in nociceptor excitation [20].

Analytical, diagnostic and therapeutic context of Accn2

• In situ hybridization evidence for the coexistence of ASIC and TRPV1 within rat single sensory neurons [20].
• RT-PCR revealed the presence of proton-gated subunits ASIC-beta and VR1 [21].
• These observations, combined with the disappearance of ASIC-ir following dorsal rhizotomy, suggest localization of ASIC to primary afferents [22].
• We have developed polyclonal antisera against ASIC, and used them to screen rat brain and spinal cord using immunocytochemistry [22].
• Two types of acid-sensing ion channel (ASIC)-like currents in cultured rat hippocampal neurons were recorded and their characteristics were studied by using a whole-cell recording technique [23].

References