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  • Title: Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.
    Author: Chen X, Gründer S.
    Journal: J Physiol; 2007 Mar 15; 579(Pt 3):657-70. PubMed ID: 17204502.
    Abstract:
    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.
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