amiloride-sensitive cation channel 2, neuronal; acid-sensing ion channel 1; ASIC1; brain Na+ channel 2; BNaC2 (ACCN2, ASIC1, BNAC2)
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Function
- cation channel with high affinity for Na+
- gated by extracellular protons
- inhibited by the diuretic amiloride
- also permeable for Ca+2, Li+ & K+
- generates a biphasic current with a fast inactivating & a slow sustained phase
- mediates glutamate-independent Ca+2 entry into neurons upon acidosis; this Ca+2 overloading is toxic for cortical neurons & may be in part responsible for ischemic brain injury
- heteromeric channel assembly seems to modulate channel properties
- functions as a postsynaptic proton receptor that influences intracellular Ca+2 concentration & CaM kinase 2 phosphorylation & thereby the density of dendritic spines
- modulates activity in the circuits underlying innate fear (putative)
- phosphorylation by PKA regulates interaction with PRKCABP & subcellular location
- phosphorylation by PKC may regulate the channel
- homotetramer or heterotetramer with other ASIC proteins (probable)
- interacts with STOM & ACCN1 (putative)
- interacts with PRKCABP
Structure
- belongs to the amiloride-sensitive Na+ channel family
Compartment
- cell membrane; multi-pass membrane protein (putative)
- localizes in synaptosomes at dendritic synapses of neurons
- colocalizes with DLG4 (putative)
Alternative splicing
named isoforms=2
Expression
- expressed in most or all neurons
Comparative biology
- the splice variant from ASIC1a described in mouse & rat, which gives rise to an isoform with different N-termini (Asic1b), does not seem to exist in human
Notes
- potentiated by Ca+2, Mg+2, Ba+2 & multivalent cations
- inhibited by anti-inflammatory drugs including salicylic acid (putative)
- potentiated by FMRFamide-related neuropeptides
- pH dependence may be regulated by serine proteases
More general terms
- transmembrane 2 protein
- amiloride-sensitive cation channel
- Na+ channel
- phosphoprotein
- evolutionary divergent protein