Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a
The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel with important physiological functions and pathophysiological impact in the central nervous system. Here we show that homomeric ASIC1a is distinguished from other ASICs by a reduced response to successive acid stimulations. Such a reduced response is called tachyphylaxis. We show that tachyphylaxis depends on H+ permeating through ASIC1a, that tachyphylaxis is attenuated by extracellular Ca2+, and that tachyphylaxis is probably linked to Ca2+ permeability of ASIC1a. Moreover, we provide evidence that tachyphylaxis is probably due to a long-lived inactive state of ASIC1a. A deeper understanding of ASIC1a tachyphylaxis may lead to pharmacological control of ASIC1a activity that could be of potential benefit for the treatment of stroke.
Molecular, Cellular and Biomedical Sciences
Journal of Physiology
Digital Object Identifier (DOI)
Chen X, Grunder S. Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a. The Journal of physiology. 2007;579(Pt 3):657-70. doi: 10.1113/jphysiol.2006.120733. PubMed PMID: 17204502; PubMed Central PMCID: PMC2151377.
© 2007 The Physiological Society