ASIC1

Description

The ASIC1 (acid sensing ion channel subunit 1) is a protein-coding gene located on chromosome 12.

ASIC1, also known as ACCN2 or BNaC2, is a protein encoded by the ASIC1 gene in humans. It belongs to a family of five genes that produce proteins forming trimeric acid-sensing ion channels (ASICs) in mammals. The ASIC1 gene has splicing variants that create different isoforms. These genes are primarily expressed in the central and peripheral nervous systems. ASICs can form both homotrimeric (identical subunits) and heterotrimeric channels. The ASIC1 protein has two transmembrane regions (TM1 and TM2), a large extracellular loop with many cysteine residues, and intracellular N and C termini. The pore of the channel is formed by the three TM2 regions of the trimer, allowing ions to flow from the extracellular space into the cytoplasm.

ASIC1 isoforms 2 and 3 act as proton-gated sodium channels. They are activated by a decrease in extracellular pH, but quickly become desensitized. The channel creates a biphasic current with a rapid inactivation phase and a slower sustained phase. It has a strong preference for sodium ions and efficiently transports lithium ions. Isoform 2 also transports potassium, but less effectively. It is nearly impermeable to rubidium and cesium ions. Isoform 3 can also transport calcium ions. It mediates calcium entry into neurons in response to acidosis, independent of glutamate. Excessive calcium accumulation is toxic to cortical neurons and may contribute to ischemic brain injury. The combination of different ASIC1 subunits within a channel can affect its properties. ASIC1 acts as a postsynaptic proton receptor, influencing intracellular calcium concentration and the phosphorylation of calmodulin-dependent protein kinase II, ultimately affecting dendritic spine density. It also modulates the activity of circuits involved in innate fear.

ASIC1 is also known as ACCN2, ASIC, BNaC2.

Associated Diseases

WES Whole Exome Sequencing