Part of the book: Neurodegenerative Diseases
Acid-sensing ion channels (ASICs) are proton-gated ion channels that are highly expressed in the nervous system and play important roles in physiological and pathological conditions. They are also expressed in non-neuronal tissues with different functions. The ASICs rapidly respond to a reduction in extracellular pH with an inward current that is quickly inactivated despite the continuous presence of protons. Recently, protons have been identified as neurotransmitters in the brain. Until now, six different isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) in rodents have been discovered and they can be assembled into homotrimers or heterotrimers to form an ion channel. Peptide toxins targeting ASICs have been found from the venoms of spider Psalmotoxin-1 (PcTx1), sea anemones (APETx2 and PhcrTx1) and snakes (MitTx and mambalgins). They reveal different pharmacological properties and are selective blockers of ASICs, except for MitTx, which is a potent activator of ASICs. In this mini review, the structure, pharmacology and effects of peptide toxins on ASICs will be introduced and their therapeutic potentials for neurological and psychological diseases will be discussed.
Part of the book: Neurotoxins