Acid-sensing ion channel

Acid-sensing ion channel

Structure of an acid-sensing ion channel

Video showing the dynamics of the acid-sensing ion channel

The acid-sensing ion channel (ASIC) is a type of ion channel that is activated by extracellular protons. These channels are primarily expressed in the central nervous system and peripheral nervous system and are involved in various physiological and pathological processes.

Structure

ASICs are part of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. They are trimeric proteins, meaning they are composed of three subunits. Each subunit has two transmembrane domains, a large extracellular loop, and intracellular N- and C-termini. The structure of ASICs has been elucidated using X-ray crystallography, revealing a complex architecture that is sensitive to changes in pH.

Function

ASICs are activated by a drop in extracellular pH, which leads to the opening of the channel and the influx of sodium ions (Na+) into the cell. This process is crucial for neuronal signaling, pain perception, and mechanosensation. ASICs are also implicated in synaptic plasticity and learning and memory.

Physiological Role

In the nervous system, ASICs contribute to the sensation of pain and touch. They are involved in the detection of tissue acidosis, which occurs during inflammation, ischemia, and muscle fatigue. ASICs are also expressed in sensory neurons where they play a role in nociception.

Pathological Implications

Dysfunction or altered expression of ASICs has been linked to various neurological disorders, including chronic pain, anxiety, and depression. ASICs are also being studied for their role in ischemic brain injury and epilepsy.

Pharmacology

ASICs are potential targets for therapeutic drugs aimed at treating pain and neurological disorders. Various inhibitors and modulators of ASICs have been identified, which can alter their activity and provide potential therapeutic benefits.

Related pages

• Ion channel
• Epithelial sodium channel
• Nociception
• Neuronal signaling