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Permeating protons contribute to tachyphylaxis of the acid‐sensing ion channel (ASIC) 1a
Author(s) -
Chen Xuanmao,
Gründer Stefan
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.120733
Subject(s) - tachyphylaxis , homomeric , acid sensing ion channel , ion channel , chemistry , extracellular , biophysics , neuroscience , pharmacology , medicine , biochemistry , biology , receptor , protein subunit , gene
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 Ca 2+ , and that tachyphylaxis is probably linked to Ca 2+ 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.