Acid-sensing ion channels: structure, function, pharmacology, and clinical significance

Area of Science:

• Neuroscience
• Physiology
• Biochemistry

Background:

• Local proton concentration changes are vital for cellular functions and linked to pathological processes.
• Acid-sensing ion channels (ASICs), part of the Epithelial Na+/degenerin (ENaC/DEG) family, sense and respond to these pH shifts.
• ASICs are low pH-activated, Na+-selective channels primarily found in the mammalian nervous system.

Purpose of the Study:

• To comprehensively review acid-sensing ion channels (ASICs).
• To cover ASICs' evolutionary origins, biophysical properties, and structure-function relationships.
• To examine ASICs' physiological and pathological roles, regulation, and pharmacology.

Main Methods:

• Literature review of existing studies on ASICs.
• Analysis of structure-function relationships, including ion permeation and channel modulation.
• Examination of experimental data, particularly from rodent models, on ASIC functions.

Main Results:

• ASICs are implicated in various physiological processes, including synaptic transmission and metabolic activity.
• ASICs play roles in fear expression, learning, pain sensation, and neurodegeneration.
• ASICs are activated by low pH and are involved in conditions like ischemia and inflammation.

Conclusions:

• ASICs are critical regulators of cellular responses to pH changes.
• Understanding ASICs is key to comprehending neurological functions and diseases.
• Further research into ASICs' regulation and pharmacology holds therapeutic potential.